Peptides (v.21, #12)

β-Amyloid precursor polypeptide in SAMP8 mice affects learning and memory by John E Morley; Vijaya B Kumar; Adonis E Bernardo; Susan A Farr; Kayoko Uezu; Nina Tumosa; James F Flood (1761-1767).
Senescence accelerated (SAMP8 [P8]) mice develop age-related deficits in memory and learning. We show that increased expression of amyloid precursor protein (APP) and its mRNA in the hippocampus are also age-related. Immunocytochemical data suggest that a critical amount of APP expression may be needed to generate amyloid (Aβ) protein plaques in the hippocampus. Deficits in acquisition and retention test performance were alleviated by administration of antibody to Aβ protein into the cerebral ventricles. This reversal of cognitive deficits provides a link between increased expression of both APP and Aβ protein and learning and memory loss in these mice.
Keywords: Beta amyloid; SAMP8 mouse; Memory; Acquisition; Amyloid precursor protein;

Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice by Vijaya B Kumar; Susan A Farr; James F Flood; Vyas Kamlesh; Mark Franko; William A Banks; John E Morley (1769-1775).
β amyloid protein (Aβ) is a 40–43 amino acid peptide derived from amyloid precursor protein (APP). Aβ has been implicated as a cause of Alzheimer’s disease (AD). Mice with spontaneous or transgenic overexpression of APP show the histologic hallmarks of AD and have impairments in learning and memory. We tested whether antisense phosphorothiolated oligonucleotides (AO) directed at the Aβ region of the APP gene given with or without antibody directed at Aβ could reverse the elevated protein levels of APP and the behavioral impairments seen in SAMP8 mice, a strain which spontaneously overexpresses APP. We found that intracerebroventricular (ICV) administration of antibody with either of two AOs directed at the midregion of Aβ improved acquisition and retention in a footshock avoidance paradigm, whereas two AOs directed more toward the C-terminal, a random AO, and vehicle were without effect. Three injections of the more potent AO given without antibody reduced APP protein levels by 43–68% in the amygdala, septum, and hippocampus. These results show that AO directed at the Aβ region of APP can reduce APP levels in the brain and reverse deficits in learning and memory.

Identification of multiple urechistachykinin peptides, gene expression, pharmacological activity, and detection using mass spectrometric analyses by Tsuyoshi Kawada; Katsuyoshi Masuda; Honoo Satake; Hiroyuki Minakata; Yojiro Muneoka; Kyosuke Nomoto (1777-1783).
Urechistachykinin I and II (Uru-TK I and II) are invertebrate tachykinin-related peptides (TRPs), which have been isolated from echiuroid worms. The cDNA sequence encoding the Uru-TK I and II revealed that the precursor also encoded five TRP-like peptides. Here, we report the characterization of these Uru-TK-like peptides named as Uru-TK III-VII. Northern and Southern blot analyses demonstrated that Uru-TK mRNA is localized in nerve tissue. In addition, the presence of the Uru-TK-like peptides as matured forms in the nerve tissue was detected by mass spectrometric analysis, and identified these peptides were shown to exhibit a contractile activity on cockroach hindgut that was as potent as that of Uru-TK II. Furthermore, synthetic Uru-TK-like peptide analogs which contained Met-NH2 instead of Arg-NH2 at their C-termini were shown to possess a potential to bind to a mammalian tachykinin receptor, indicating that Uru-TK-like peptides are likely to correspond to vertebrate tachykinins, except for the difference at the C-terminal residue. These findings show that Uru-TK-like peptides are essentially equivalent to Uru-TK I and II, leading to the proposal that Uru-TK-like peptides play an essential role as invertebrate tachykinin neuropeptides.
Keywords: Tachykinin; Invertebrate neuropeptide; Uru-TK; Urechis unicinctus; Mass spectrometry;

Multiple molecular forms of glucagon and insulin in the kaluga sturgeon, Huso dauricus by Tadashi Andoh; Hiromichi Nagasawa; Takahiro Matsubara (1785-1792).
Five molecular forms of glucagon and two molecular forms of insulin were characterized from the kaluga sturgeon. Substitutions occurred at two to thirteen internal amino acid residues among the five molecular forms of glucagons, indicating that these glucagons were encoded by five distinct genes. The amino acid sequences of two insulins from the kaluga sturgeon were identical to those of paddlefish insulin-II and Russian sturgeon insulin except that kaluga sturgeon insulin-I had an extension of five residues at the B-chain N-terminus. This is the first demonstration that more than two molecular forms of glucagon have been characterized from a single animal species.
Keywords: Kaluga sturgeon; Huso dauricus; Chondrostei; Insulin; Glucagon; Amino acid sequence; Primary structure; Tetraploidy; Gene amplification;

Structure-activity relationships of trout bradykinin ([Arg0,Trp5,Leu8]-bradykinin]) by Jorgen Jensen; Ana Maria Soto; J.Michael Conlon (1793-1798).
Trout bradykinin ([Arg0,Trp5,Leu8]-BK) produces sustained and concentration–dependent contractions of isolated longitudinal smooth muscle from trout stomach, although mammalian BK is without effect. Circular dichroism studies have demonstrated that trout BK, unlike mammalian BK, does not adopt a stable β-turn conformation, even in the presence of sodium dodecyl sulfate (SDS) or trifluoroethanol. The myotropic actions of a series of analogs in which each amino acid in trout BK was replaced by either alanine or the corresponding D-isomer were investigated. The peptides with Ala4, D-Pro3, D-Trp5, D-Ser6, and D-Pro7 substitutions were inactive and did not act as antagonists of trout BK. The analog with [Ala5] was a weak partial agonist. The substitution (Arg0 → Ala) led to >50-fold decrease in potency but, in contrast to the importance of Phe8 in both BK and desArg9-BK in activating the mammalian B2 and B1 receptors respectively, substitutions at Leu8 in trout BK had only a minor effect on potency. Antagonists to the mammalian B2 receptor generally contain a D-aromatic amino acid at position 7 of BK but the analog [Arg0,Trp5,D-Phe7,Leu8]-BK was a weak agonist at the trout receptor. Similarly, the potent nonpeptide mammalian B2 receptor antagonist FR173657 was without effect on the action of trout BK. These data suggest the hypothesis that the receptor binding conformation of trout BK is defined by the central region (residues 3–7) of the peptide but is adopted only upon interaction with the receptor. The bioactive conformation is probably stabilized by an ionic interaction between Arg0 in the peptide and an acidic residue in the receptor.
Keywords: Bradykinin; Trout stomach; B2 receptor; B1 receptor; Smooth muscle;

Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa by Yasunari Muramatsu; Kouhei Fukushima; Kazumi Iino; Kazuhito Totsune; Kazuhiro Takahashi; Takashi Suzuki; Gen Hirasawa; Junji Takeyama; Mitsuko Ito; Masato Nose; Atsushi Tashiro; Michio Hongo; Yutaka Oki; Hiroshi Nagura; Hironobu Sasano (1799-1809).
Urocortin is a newly identified member of the CRF neuropeptide family. Urocortin has been found to bind with high affinity to CRF receptors. The present study investigated urocortin and CRF receptor expression in human colonic mucosa. Non-pathologic sections of adult colorectal tissues were obtained from patients with colorectal cancer at surgery. Urocortin expression was examined using immunohistochemistry and messenger (m) RNA in situ hybridization. Isolated lamina propria mononuclear cells (LPMC) and epithelial cells were also analyzed by flow cytometry for the characterization of urocortin-positive cells, and by RT-PCR for detection of urocortin, CRF, and CRF receptor mRNA. Urocortin peptide distribution at various stages of human development (n = 35, from 11 weeks of gestation to 6 years of age) was examined by immunohistochemistry using surgical and autopsy specimens. Immunoreactive urocortin and urocortin mRNA were predominantly detected in lamina propria macrophages. Urocortin peptide expression was detected from as early as three months of age, but not before birth or in neonates. Urocortin, CRF receptor type 1 and type 2α mRNA were detected in LPMC. CRF receptor type 2β mRNA, a minor isoform in human tissues, was also detected in LPMC, but at lower levels. Urocortin is locally synthesized in lamina propria macrophages and may act on lamina propria inflammatory cells as an autocrine/paracrine regulator of the mucosal immune system. The appearance of urocortin after birth indicates that the exposure to dietary intake and/or luminal bacteria after birth may contribute to the initiation of urocortin expression in human gastrointestinal tract mucosa.
Keywords: Urocortin; CRF receptor; Colon; Macrophage;

Activation of urocortin transport into brain by leptin by Abba J Kastin; Victoria Akerstrom; Weihong Pan (1811-1817).
There are several transport systems for peptides and polypeptides at the blood-brain barrier (BBB) which facilitate the passage of bioactive substances from blood to brain or from brain to blood. Nonetheless, it would be a novel concept for one peptide or polypeptide to activate the transport of another peptide with a similar function but unrelated structure. In this study, we report the first observation of such a phenomenon: activation of a urocortin transport system at the BBB by leptin. Urocortin, a corticotropin-releasing factor (CRF)-related neuropeptide, is a more potent suppressor of food intake than leptin or CRF when injected peripherally. Radiolabeled urocortin (125I-urocortin) was used for these in vivo studies in mice; it remained stable and intact during the experimental period. Unlike CRF, urocortin was not saturably transported out of the brain. There was no substantial entry of 125I-urocortin into brain as determined by sensitive multiple-time regression analysis after iv bolus injection. Addition of leptin, however, caused a dose-related increase in the influx of 125I-urocortin and greatly facilitated its entry into brain parenchyma; this effect disappeared at higher doses of leptin. Moreover, in the presence of an activating dose of leptin, the entry of 125I-urocortin into brain was saturable. The results indicate that the presence of leptin contributes to the potent satiety effects of urocortin after peripheral administration. Thus, the action of leptin in the periphery extends beyond its direct passage across the BBB and involves acute modulation of an inert transport system. We believe that these findings have broad physiological implications and indicate a unique function of the BBB as a regulatory interface.
Keywords: Urocortin; Leptin; Blood-brain barrier; Corticotropin-releasing factor; Satiety; Hypothalamus; Peptide; Transport;

Fetal lung produces corticotropin-releasing hormone (CRH) without known direct effects. We tested the hypothesis that CRH can directly regulate lung development. In baboon fetal lung explants, CRH strongly induces surfactant phospholipid synthesis and SP-C immunostaining, plus [3H]thymidine incorporation. CRH receptor mRNA was detected in lung from multiple baboons at e125. Testing thyrotropin (TRH) as a specificity control, we did demonstrate different direct effects with only modest stimulation of surfactant phospholipid synthesis and strong induction of cytidylyltransferase gene expression. Therefore, CRH, similar to ACTH and glucocorticoids, is a potent inducer of cell differentiation in fetal lung.
Keywords: Lung development; Dexamethasone; Surfactant phospholipid synthesis; Surfactant protein C; Cell proliferation;

The effects of retinoic acid (RA) on lung cancer cells were investigated. Both all-trans (t-RA) and 13-cis RA (c-RA) decreased specific 125I-VIP binding to NCI-H1299 cells in a time- and concentration-dependent manner. After 20 hr, 30 μM t-RA decreased specific 125I-VIP binding by 60%. By Scatchard analysis, the density of VIP binding sites but not the affinity was reduced by 42%. NCI-H1299 VPAC1 receptor mRNA was reduced by 48%. VIP caused a 3-fold elevation in the NCI-H1299 cAMP, and the increase in cAMP caused by VIP was reduced by 38% if the NCI-H1299 cells were treated with t-RA. Using the MTT assay, 3 μM t-RA and 3 μM c-RA inhibited NCI-H1299 proliferation by 60 and 23% respectively. Also, transforming growth factor (TGF)-β2 increased after treatment of NCI-H1299 cells with t-RA whereas TGF-β1 mRNA was unaffected and TGF-β3 mRNA was decreased. These results suggest that RA may inhibit lung cancer growth by down-regulating VPAC1 receptor and TGF-β3 mRNA but up-regulating TGF-β2 mRNA.
Keywords: retinoic acid; VIP receptors; cAMP; transforming growth factor β; lung cancer;

Immunization with a novel HIV-1-Tat multiple-peptide conjugate induces effective immune response in mice by Robert A. Boykins; Jeanette A. Ardans; Larry M. Wahl; Renu B. Lal; Kenneth M. Yamada; Subhash Dhawan (1839-1847).
We report here a novel, highly immunogenic synthetic, multiple-peptide conjugate comprising functional domains Tat21–40 and Tat53–68 from HIV-1 group M plus Tat9–20 from HIV-1 group O of the HIV-Tat protein (HIV-1-Tat-MPC). Vaccination of mice with HIV-1-Tat-MPC induced an effective immune response to all three functional domains. The anti-HIV-1-Tat-MPC antibodies efficiently inhibited Tat-induced viral activation in monocytes infected with HIVBa-L as well as with various clinical HIV-1 isolates, and reduced Tat-mediated cytopathicity in infected cells by 60–75%. Our results indicate that anti-HIV-1-Tat-MPC antibodies inhibit viral pathogenesis, possibly by blocking functional determinants of Tat and disrupting autocrine and paracrine actions of secreted Tat protein. This epitope-specific, synthetic Tat construct may, therefore, provide a subunit AIDS vaccine candidate for inducing an effective immunoprophylaxis response to reduce progression of HIV infection.
Keywords: Monocytes; Macrophages; HIV-1-Tat; HIV; AIDS; Pathogenesis; Vaccine;

New conformationally restricted analog of the immunosuppressory mini-domain of HLA-DQ and its biological properties by Zbigniew Szewczuk; Andrzej Wilczyński; Marcin Dyba; Inga Petry; Ignacy Z Siemion; Zbigniew Wieczorek (1849-1858).
Our previous studies revealed that the nonapeptide fragment of HLA-DQ located in the β164–172 loop of the Thr-Pro-Gln-Arg-Gly-Asp-Val-Tyr-Thr sequence suppresses the immune humoral and cellular responses . Based on the crystal structure of HLA-class II molecules we designed and synthesized a cyclic analog with restricted conformation, cyclo(Suc-Thr-Pro-Gln-Arg-Gly-Asp-Val-Lys)-Thr-OH (Suc = succinyl) by reacting a Lys side chain with a succinylated N-terminus. The cyclization product more potently suppresses the cellular immune response than its linear counterparts and is efficiently cleaved by trypsin. The results indicate that the β164–172 loop may serve as a functional epitope on the HLA class II surface for intermolecular binding.
Keywords: Histocompatibility antigen; Thymopentin analogs; Immunosuppressors; RGD sequence; Cyclic peptide analog; Proteolytic stability;

Presence of immunoreactive adrenomedullin in human and bovine milk by Ruben Pio; Alfredo Martı́nez; Ted H Elsasser; Frank Cuttitta (1859-1863).
We examined by radioimmunoassay the presence of immunoreactive adrenomedullin (ir-AM) in human and bovine milk. Milk samples displaced 125I-AM from the AM-antiserum in parallel to the standard curve. RP-HPLC revealed a main immunoreactive peak eluting as synthetic AM. Concentrations in human milk ranged between 140 and 404 pg/mL. In cow, the levels of AM were 73.5 ± 3.8 pg/mL. Bovine milk products had AM levels similar to those found in fresh bovine milk. Human milk had growth promoting activity on the human intestinal cell line Int-407 that could be partially blocked with an anti-AM antibody.
Keywords: Adrenomedullin; Radioimmunoassay; Human milk; Bovine milk; Intestine 407;

Expression of nociceptin/OFQ receptor and prepro-nociceptin/OFQ in lymphoid tissues by Mary S. Pampusch; Janet R. Serie; Mark A. Osinski; Virginia S. Seybold; Michael P. Murtaugh; David R. Brown (1865-1870).
This study was undertaken to examine the presence of functional nociceptin/orphanin FQ (N/OFQ) receptors in the immune system. Receptor mRNA signals were detected by RT-PCR in porcine thymus, lymph nodes, spleen and freshly-isolated splenocytes; the distribution of prepro-nociceptin/-orphanin FQ (PP-N/-OFQ) mRNA was similar, with the exception of lymph nodes. However, specific [3H]nociceptin binding sites were not detected in rat or porcine lymphoid tissues, and 0.1–100 nM nociceptin had no effect on forskolin-stimulated cyclic AMP concentrations in porcine splenocytes. Thus, it appears that nociceptin/orphanin FQ receptor mRNA, but not a functional receptor protein is expressed in the immune system.
Keywords: Rat; Pig; Spleen; Intestine; mRNA-protein mismatch;

Dissociation of analgesic and rewarding effects of endomorphin-1 in rats by Aimee M Wilson; R.Denis Soignier; James E Zadina; Abba J Kastin; William L Nores; Richard D Olson; Gayle A Olson (1871-1874).
The μ-receptor is the primary mediator of the effects of morphine and the endogenous opiates, endomorphin-1 and endomorphin-2. Here we demonstrate a dissociation of the analgesic and rewarding effects of endomorphin-1 in rats. Tail-flick results revealed that endomorphin-1 produced significant analgesic effects within 10-min after injection. However, it failed to show reward properties in the standard 45- min conditioned place preference (CPP) paradigm or in an abbreviated 10-min pairing which paralleled the time frame of the tail-flick findings. Morphine induced both analgesia and reward. Endomorphin-1 therefore is the first mu opiate shown to produce potent analgesia in the absence of reward behavior, and thus may have significant clinical potential.

Acetyl-RYYRIK-NH2 is a highly efficacious OP4 receptor agonist in the cardiovascular system of anesthetized rats by Barbara Malinowska; Hanna Kozłowska; Hartmut Berger; Eberhard Schlicker (1875-1880).
Nociceptin, the endogenous ligand of the OP4 or ORL1 (opioid receptor-like1) receptor, decreases blood pressure and heart rate in anesthetized rats. Since the OP4 receptor antagonist [Phe1Ψ(CH2-NH)Gly2]-nociceptin(1–13)NH2 possesses an agonistic effect in this model, we examined whether other purported OP4 receptor antagonists, acetyl-RYYRIK-NH2 and naloxone benzoylhydrazone, antagonize the depressant effects of nociceptin. Acetyl-RYYRIK-NH2, like nociceptin and [Phe1Ψ(CH2-NH)Gly2]-nociceptin(1–13)NH2 and unlike naloxone benzoylhydrazone, decreased diastolic blood pressure and heart rate (rank order of potencies: nociceptin ≈ acetyl-RYYRIK-NH2 ≫ [Phe1Ψ(CH2-NH)Gly2]-nociceptin(1–13)NH2). The depressant effects were insensitive to the OP1–3 receptor antagonist naloxone but diminished by naloxone benzoylhydrazone. In conclusion, the hypotensive and bradycardic effects of nociceptin in the anesthetized rat are mediated via OP4 receptors, at which acetyl-RYYRIK-NH2 is a highly potent and efficacious agonist.
Keywords: Nociceptin ORL1 receptor; OP4 receptors; [Phe1Ψ(CH2-NH)Gly2]-nociceptin(1–13)NH2; Acetyl-RYYRIK- NH2; Naloxone benzoylhydrazone; Cardiovascular system;

The role of hippocampal dynorphin A (1–8) (Dyn A (1–8)) and kappa opioid receptors was investigated in the isolation-induced hypertensive rat (IHR). Male Sprague Dawley rats were either isolated (1 per cage) or grouped (3 per cage) for 7 days. Isolated rats exhibited increased blood pressure (systolic blood pressure 159.7 ± 6.6 mmHg) whereas the grouped rats remained normotensive (systolic blood pressure 137 ± 6.3 mmHg). Using radioligand binding techniques we observed a significant increase in kappa opioid receptor binding in the hippocampus of isolated rats (56% increase) and this further increased when the length of isolation was increased to 2 weeks (72% increase). Radioimmunoassay showed that isolation decreased the hippocampal content of Dyn A (1–8) from 12.7 ± 0.4 to 11.6 ± 0.2 pg Dyn A (1–8) per 10 mg tissue (rats weighing approximately 100 g) and from 13.3 ± 0.8 to 9.7 ± 1 pg Dyn A (1–8) per 10 mg tissue (approximately 200 g rats). These data suggest that functional alterations in the hippocampal dynorphin system may be involved in the maintenance of isolation induced hypertension.
Keywords: Hypertension; Isolation; Hippocampus; Dynorphin A; Kappa-opioid receptor;

Differently labeled peptide ligands for rapid investigation of receptor expression on a new human glioblastoma cell line by Marlies Fabry; Chiara Cabrele; Hartwig Höcker; Annette G Beck-Sickinger (1885-1893).
The neuropeptides vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and substance P (SP) as well as insulin and insulin-like growth factor 1 (IGF-1) were labeled with biotin, fluorescent dyes, and radioactivity to characterize the expression of peptide receptor of a novel cancer cell line, established from a human glioblastoma multiforme. Thus, not only binding sites could be detected but advantages and disadvantages of the different labels could be compared, too. With all three markers, the presence or absence of the receptors could be answered rapidly and sensitively. The glioblastoma cells express receptors for VIP (IC50 = 9 nM ± 30%), insulin (K d = 0.66 nM ± 14%, B max = 0.028 nM ± 13%), and IGF-1 (K d = 21 nM ± 25%, B max = 1.65 nM ± 24%), but there are no binding sites for NPY and SP. As especially VIP and IGF-1 receptors are expressed in huge amounts, these receptors might be an interesting target for tumor diagnostics and therapy.
Keywords: Biotin and fluorescence labeling; Neuropeptides; Vasointestinal peptide (VIP); Insulin-like growth factor 1 (IGF-1); Insulin; Glioblastoma cells;

The present study was aimed to test the hypothesis that increased endogenous CCK may interact with the anorectic serotonergic agent dl-fenfluramine to reduce food intake in rats. Previous studies, using selective CCK receptor antagonists, could demonstrate CCK-dependent 5-HT-induced anorexia. In the present approach, we used protease inhibitors to increase levels of endogenous CCK instead of blocking CCK receptors by antagonists. The protease inhibitors we used were soybean trypsin inhibitor (STI) and camostate. We hypothesized that combining the anorectic serotonergic drug dl-fenfluramine with either STI or camostate should result in an enhanced hypophagic effect when compared to single drug treatment. All feeding experiments were performed in non-deprived rats during night time feeding. Given alone, STI (500 mg/kg, po), camostate (200 mg/kg po) and also fenfluramine (1–9 mg/kg ip) reduced significantly food intake, with a more pronounced effect following fenfluramine. However, the experiments do not provide evidence for any additive or synergistic action between camostate or STI and the anorectic serotonergic drug dl-fenfluramine on food intake.
Keywords: Fenfluramine; Soybean trypsin inhibitor; Camostate; Feeding; Rat; CCK; Serotonin;

The kallikrein-kininogen-kinin system: lessons from the quantification of endogenous kinins by Charles Blais; François Marceau; Jean-Lucien Rouleau; Albert Adam (1903-1940).
The purpose of the present review is to describe the place of endogenous kinins, mainly bradykinin (BK) and des-Arg9-BK in the kallikrein-kininogen-kinin system, to review and compare the different analytical methods reported for the assessment of endogenous kinins, to explain the difficulties and the pitfalls for their quantifications in biologic samples and finally to see how the results obtained by these methods could complement and extend the pharmacological evidence of their pathophysiological role.
Keywords: Analytical methods; Cardioprotection; Endogenous kinins; Inflammation; Kallikrein-kininogen-kinin system; Metabolism;

Study of the communication between nervous and immune systems culminated in the understanding that cytokines, formerly considered exclusively as immune system-derived peptides, are endogenous to the brain and display central actions. More recently, immune cells have been recognized as a peripheral source of “brain-specific” peptides with immunomodulatory actions. This article reviews studies concerning reciprocal effects of selected cytokines and neuropeptides in the nervous and immune systems, respectively. The functional equivalence of these two categories of communicators is discussed with reference to the example of the actions of neuropeptide somatostatin in the immune system.
Keywords: Neuropeptides; Lymphocytes; Macrophages; NK cells; Proliferation; Cytokine and immunoglobulin secretion; Somatostatin; Neuro-immune modulation;

Stroke is the leading cause of long-term disability in the United States and affects more people than any other neurologic disorder. Hypertension is a major risk factor associated with stroke. Several anti-hypertensive agents have been used to treat chronic hypertension to reduce the morbidity and mortality of stroke. Previous experimental studies have shown reduced stroke mortality with angiotensin-converting enzyme (ACE) inhibitors. This review discusses the development of stroke and potential use of ACE inhibitors in prevention and treatment of this disease. Furthermore, this review focuses on current investigations aimed at cellular mechanisms involved in stroke-induced microvascular alterations.
Keywords: Stroke; ACE inhibitors; Cellular mechanisms; Hypertension; Hypoxia/reoxygenation;

Endogenous opiates: 1999 by Anthony L Vaccarino; Abba J Kastin (1975-2034).
This paper is the twenty-second installment of the annual review of research concerning the opiate system. It summarizes papers published during 1999 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; learning, memory, and reward; eating and drinking; alcohol and other drugs of abuse; sexual activity, pregnancy, and development; mental illness and mood; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; gastrointestinal, renal, and hepatic function; cardiovascular responses; respiration and thermoregulation; and immunologic responses.
Keywords: Stress; Tolerance; Dependence; Learning; Memory; Reward; Eating; Drinking; Alcohol; Mental illness; Depression; Activity; Cardiovascular responses; Temperature; Respiration; Epilepsy; Sex; Immunology; Opiate; Peptide;

Index (2037-2041).

Index (2043-2047).