Peptides (v.21, #2)

Immunocytes from the mollusc Mytilus galloprovincialis express corticotropin-releasing hormone (CRH) receptor subtype (CRH-R1 and CRH-R2)-like mRNAs. Using computer-assisted microscopic image analysis, we have found that exogenous CRH provokes changes in the cellular shape of immunocytes, and that this response is extracellular Ca2+-dependent. The various inhibitors of transduction signaling pathways, i.e. suramin sodium, 2′,5′-dideoxyadenosine, neomycin sulfate, calphostin C, H-89, and wortmannin, completely or partially inhibit these changes. The present findings demonstrate that PKA, PKC, and PKB/Akt are involved in CRH-induced cell shape changes in immunocytes, and that the cellular effect of CRH needs the synergistic action of the two second messengers, cAMP and IP3.
Keywords: Molluscs; Immunocytes; CRH; cAMP; IP3; Signal transduction pathways;

Distribution of PACAP-like immunoreactivity in the nervous system of oligochaeta☆ by D Reglödi; I Lengvari; M Szelier; S Vigh; A Arimura (183-188).
The marked similarity between the primary structures of human, other vertebrate, and the invertebrate tunicate PACAP suggests that PACAP is one of the most highly conserved peptides during the phylogeny of the metazoans. We investigated the distribution of PACAP-like immunoreactivity in the nervous system of three oligochaete (Annelida) worms with immunocytochemistry. The distribution pattern of immunoreactivity was similar in all three species (Lumbricus terrestris, Eisenia fetida, and Lumbricus polyphemus). The cerebral ganglion contains numerous immunoreactive cells and fibers. A few cells and fibers were found in the medial and lateral parts of the subesophageal and ventral cord ganglia. In the peripheral nervous system, immunoreactivity was found in the enteric nervous system, in epidermal sensory cells, and in the clitellum.
Keywords: Immunoreactivity; Cerebral ganglion; Neuropeptides; Peripheral nervous system;

Proctolin caused dose-dependent (1–200 nM) contraction of the isolated hindgut of S. gregaria which was abolished by [α-methyl-L-tyrosine2]-proctolin (1 μM). In comparison, cycloproctolin (5 μM) reduced the proctolin maximum response by 41%. Hindgut homogenates contained [3H]proctolin binding sites with a K d value of 660 nM, a B max value of 23.8 pmol/mg protein and a Hill coefficient of 0.934. Cycloproctolin (IC50, 220 nM; K i, 204 nM), unlabeled proctolin (IC50 680 nM) and [α-methyl-L-tryosine2]-proctolin (IC50 3.1 μM, K i , 2.9 μM) but not SchistoFLRFamide (1 nM–10 μM) were capable of displacing bound [3H]proctolin.
Keywords: Schistocerca gregaria; Receptor; Bioassay; Binding; Proctolin antagonists; Neuropeptide;

New N-terminal analogs of the peptide HVFLRFamide, the minimum sequence of the insect myosuppressins capable of inhibiting spontaneous and induced contractions of the locust oviduct, were synthesized and tested for biologic activity on locust oviduct. Most active, as judged by the ability to inhibit proctolin-induced contractions of locust oviduct, was (N α-acetyl)-HVFLRFamide. D-Pro-HVFLRFamide was also highly inhibitory. Interestingly, low doses of the pentapeptide analog (N α-imidazoleacrylyl)-VFLRFamide inhibited oviduct contractions. This is the first pentapeptide analog shown to inhibit contractions of locust oviduct, and this result indicates that the α-amino group of His is not absolutely required for inhibitory activity. In all cases when His was replaced by a d-amino acid, the analogs were stimulatory, resulting in an increase in basal tonus of the locust oviduct. The results provide further insight into the structural features of the HVFLRFamide molecule that are required for inhibitory activity on locust oviduct muscle.
Keywords: Structure-activity relationships; Inhibiting neuropeptides; Muscle contraction; Locust; Oviduct;

Neuropeptide FF (NPFF), an endogenous opioid-related neuromodulater, has been reported to show significant effects on the cardiovascular system, namely elevation of arterial blood pressure (BP) and heart rate (HR) in rats. In the present study, we synthesized two novel NPFF analogs, PFRFamide (putative NPFF agonist) and PFR(Tic)amide (putative NPFF antagonist), and examined their cardiovascular effect on BP and HR in anesthetized rats. The arterial mean BP and HR were measured by way of direct femoral artery catheterization. The data showed that PFRFamide increased BP in a dose-dependent manner, while PFR(Tic)amide decreased BP dose-dependently. These results revealed the possibility of PFRFamide and PFR(Tic)amide to be NPFF agonist and antagonist (or inverse agonist), respectively. These two NPFF analogs may possess potential in new drug design, and the NPFF system could be very important in mammalian cardiovascular function.
Keywords: Neuropeptide FF; Blood pressure; Heart rate; Neuropeptides;

The proopiomelanocortin (POMC)-derived peptides are important regulators in a number of central nervous system pathways especially as they relate to food intake as well as metabolic and autonomic responses. In this study, we investigated the sympathetic nervous and cardiovascular responses to intracerebroventricular (i.c.v.) administration of alpha melanocyte stimulating hormone (αMSH), β-endorphin (β-END) and adrenal corticotrophic hormone (ACTH) alone or in the presence of a melanocortin antagonist, or an opioid antagonist, in normal animals. The i.c.v. administration of αMSH and ACTH resulted in a significant increase in the lumbar sympathetic nerve activity (LSNA) that was accompanied by an increase in mean arterial pressure (MAP). On the other hand i.c.v. administration of β-END decreased the LSNA and MAP. The pretreatment of animals with the melanocortin-4 (MC-4) receptor antagonist, agouti protein, significantly antagonized the response to αMSH and also, paradoxically, not only antagonized the response to β-END but converted its inhibitory responses on both the LSNA and MAP to a sympathetic activated and pressor response. Pretreatment with the opioid antagonist, naloxone, significantly antagonized the sympathetic nervous and cardiovascular response to β-END. It partially but significantly antagonized the MAP response to αMSH, but the sympathetic response was unaffected. Neither agouti protein nor naloxone altered the sympathetic nervous and cardiovascular response to ACTH. From these studies, we conclude that i.c.v. administration of αMSH and ACTH increases the LSNA and cardiovascular dynamics, whereas β-END decreases it. And, the MC-4 receptor antagonist reverses the endorphin response and the opioid antagonist attenuates the αMSH response suggesting possible receptor or central neural pathway interactions between MC-4 and the opioid receptor mediated effects.
Keywords: Proopiomelanocortin; αMSH; β-Endorphin; ACTH; Sympathetic activity; Mean blood pressure; Agouti protein;

Interaction of α-melanotropin (α-MSH) and noradrenaline in the median eminence in the control of female sexual behavior☆ by Teresa Scimonelli; Favio Medina; Catherine Wilson; Marı́a Ester Celis (219-223).
In the present study, we examined the effects of the injection of α-melanotropin (α-MSH), noradrenaline (NA), and dopamine in the median eminence of ovariectomized-adrenalectomized rats on female sexual behavior. The animals were primed with l0 μg of estradiol benzoate, and 52–54 h later they were injected into the median eminence with either 1 μl of artificial cerebrospinal fluid, 1 μg/rat α-MSH, 200 ng/rat NA, 200 ng or 2 μg/rat dopamine, in 1 μl of artificial cerebrospinal fluid. Both α-MSH and NA significantly stimulated sexual behavior. This effect was antagonized by two β-adrenergic antagonists: propranolol (500 ng/rat) and metoprolol (400 ng/rat) applied 15 min before the α-MSH or NA. The α-adrenergic antagonist prazosine (500 ng/rat) was ineffective in reducing the effect of α-MSH. The vehicle and dopamine at both doses had no effect on sexual activity. These results indicate that α-MSH and NA in the median eminence stimulate female sexual behavior and that NA mediates the action of α-MSH via β-receptors.
Keywords: α-MSH; Noradrenaline; Female sexual behavior; Median eminence;

Preprotachykinin gene expression in goldfish brain: by P Peyon; H Saied; X Lin; R.E Peter (225-231).
Recently, we described the complete nucleotide sequence of γ-preprotachykinin (γ-PPT) mRNA and the deduced amino acid sequence of the precursor on the basis of molecular cloning and sequence analysis of cDNA from goldfish brain. In the present study, γ-PPT gene expression in the brain of goldfish was examined using quantitative Northern blot analysis. The results showed that the γ-PPT gene is highly but differentially expressed in the olfactory bulbs, hypothalamus, and posterior brain regions. There are sexual dimorphism and seasonal variations in γ-PPT gene expression. In addition, the postprandial changes in γ-PPT gene expression in the olfactory bulbs and hypothalamus suggest that tachykinin peptides are involved in regulation of feeding behavior in goldfish.
Keywords: Tachykinin; Feeding; Seasonal variation; Brain; Goldfish;

Amylin receptors mediate the anorectic action of salmon calcitonin (sCT) by T.A Lutz; S Tschudy; P.A Rushing; E Scharrer (233-238).
The teleost salmon calcitonin (sCT), but not mammalian CT, shows similar biologic actions in the skeletal muscle as amylin and calcitonin gene-related peptide (CGRP). The peptides have also been shown to reduce food intake in rats. Because sCT, but not amylin, binds irreversibly to amylin binding sites, the aim of the present study was to compare the anorectic potency of both peptides. To determine whether sCT reduces food intake through interaction with amylin binding sites, we also tested whether appropriate antagonists (CGRP 8–37, AC 187) attenuate the anorectic effect of sCT. Finally, we wanted to know whether rat calcitonin (rCT) and sCT reduce food intake to the same extent. Peptides were injected intraperitoneally at dark onset in 24 h food-deprived rats. At doses of 5 or 0.5 μg/kg, the anorectic effect of sCT was more potent and lasted much longer (e.g. 5 μg/kg: sCT > 10 h; amylin approx. 2 h) than that of amylin. Both CGRP 8–37 and AC 187 (10 μg/kg) markedly reduced the anorectic action of sCT (0.5 μg/kg). In contrast to sCT, rCT (0.5 μg/kg) had no effect on food intake. It is concluded that sCT’s anorectic effect is partly mediated by amylin receptors. Irreversible binding of sCT to amylin receptors may lead to a stronger and prolonged effect in comparison to amylin due to a sustained activation of the binding sites. Similar to other actions of CTs, the anorectic potency of sCT in rats was higher than that of mammalian (rat) CT. This agrees with binding profiles of amylin, sCT, and rCT at amylin binding sites as observed in in vitro studies.
Keywords: Amylin; Salmon calcitonin; Rat calcitonin; Food intake; Amylin/sCT receptors; RAMP;

New highly specific agonistic peptides for human melanocortin MC1 receptor☆ by Michael Szardenings; Ruta Muceniece; Ilze Mutule; Felikss Mutulis; Jarl E.S. Wikberg (239-243).
A peptide with very high specificity for the human melanocortin MC1 receptor identified by phage display was used as a lead for the design of new peptides. Two new peptides, MS05 and MS09, were synthesized and found to bind with sub-nanomolar affinities to the MC1 receptor. Both these peptides showed strong agonistic activity at the MC1 receptor. The MS05 was the most MC1 receptor selective as it showed virtually no binding affinity for the MC4 and MC5 receptors and only micromolar affinity for the MC3 receptor. The selectivity and potency of the new peptides make them potent tools for studies of MC1 receptors, as well as novel potential candidate drugs for the treatment of inflammatory conditions.
Keywords: Melanocortin receptors; Melanocyte stimulating hormone; Receptor selective peptides;

Binding sites for melanin-concentrating hormone in the human brain by Masahiko Sone; Kazuhiro Takahashi; Osamu Murakami; Kazuhito Totsune; Zenei Arihara; Fumitoshi Satoh; Hironobu Sasano; Hisao Ito; Toraichi Mouri (245-250).
Binding sites for melanin-concentrating hormone (MCH) in human brain were investigated and characterized by radioligand binding. Specific binding sites for MCH were present in every region of human brain (cerebral cortex, cerebellum, thalamus, hypothalamus, pons, and medulla oblongata) obtained at autopsy. α-Melanocyte stimulating hormone or ACTH was a poor inhibitor of 125I-MCH binding (IC50 > 1 μM) compared with MCH (IC50 = 0.3 ± 0.07 nM, mean ± SEM, n = 3). Scatchard plots of 125I-MCH binding in human brain (thalamus) gave a dissociation constant of 0.2 ± 0.06 nM and maximal binding of 5.8 ± 0.3 fmol/mg protein (n = 3). These findings suggest that specific MCH binding sites that differ from the melanocortin receptors exist in human brain.
Keywords: Melanin-concentrating hormone; Receptor; Human brain; Melanocortin;

Production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1, by cultured human adrenocortical carcinoma cells by Kazuhiro Takahashi; Ayako Yoshinoya; Osamu Murakami; Kazuhito Totsune; Shigeki Shibahara (251-256).
The production and secretion of peptides by adrenocortical tumors have not been well studied. We therefore studied the production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1 in SW-13 human adrenocortical carcinoma cells by radioimmunoassay and Northern blot analysis. Both immunoreactive-adrenomedullin and immunoreactive-endothelin were detected in the culture medium of SW-13 cells (27.7 ± 1.6 fmol/10 5 cells/24 h and 11.0 ± 0.8 fmol/10 5 cells/24 h, respectively, mean ± SEM, n = 6). Northern blot analysis showed the expression of adrenomedullin mRNA and endothelin-1 mRNA in SW-13 cells. On the other hand, no significant amount of calcitonin gene-related peptide, corticotropin-releasing hormone, neuropeptide Y, or urocortin was secreted by SW-13 cells. Treatment with ACTH (10−9–10−7 mol/l), angiotensin II (10−9–10−7 mol/l), or dexamethasone (10−8–10−6 mol/l) for 24 h had no significant effects on immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium of SW-13. Treatment with tumor necrosis factor (TNF)-α (20 ng/ml) increased significantly both immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium. Interferon-γ (100 U/ml) increased the immunoreactive-endothelin levels, but not immunoreactive-adrenomedullin levels, whereas interleukin-1 (IL-1)β (10 ng/ml) increased immunoreactive-adrenomedullin levels, but not immunoreactive-endothelin levels. These findings indicate that SW-13 human adrenocortical carcinoma cells produce and secrete two vasoactive peptides, adrenomedullin, and endothelin-1 and that the secretion of these two peptides is modulated differently by cytokines.
Keywords: Adrenocortical tumors; Tumor necrosis factor; Calcitonin gene-related peptide; Corticotropin-releasing hormone; Neuropeptide Y; Urocortin;

Effects of adrenomedullin and PAMP on membrane potential and neurotransmission☆ by Kenichi Goto; Koji Fujii; Uran Onaka; Isao Abe; Masatoshi Fujishima (257-263).
The effects of adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) on membrane potential and sympathetic neurotransmission were studied in rat mesenteric arteries by using microelectrodes. AM (10−7 M) but not PAMP (10−6 M) produced membrane hyperpolarization, which was abolished by high K solution or by glibenclamide, an ATP-sensitive K+ (KATP) channel blocker. Neither AM nor PAMP affected excitatory junction potentials, a measure of sympathetic, purinergic neurotransmission. These findings suggest that AM hyperpolarizes the membrane via activation of KATP channels, which may contribute to the vasodilatory action of AM, whereas the mechanisms of the vasodepressor action of PAMP remain unclear.
Keywords: Adrenomedullin; Proadrenomedullin N-terminal 20 peptide; ATP-sensitive K+-channels; Sympathetic neurotransmission; Mesenteric artery; Rat;

Immunohistochemical localization and distribution of VIP/PACAP receptors in human lung☆ by Rebeca Busto; Juan C Prieto; Guillermo Bodega; José Zapatero; Isabel Carrero (265-269).
VIP and PACAP are distributed in nerve fibers throughout the respiratory tract acting as potent bronchodilators and secretory agents. By using RT-PCR and immunoblotting techniques, we have previously shown the expression of common VIP/PACAP (VPAC1 and VPAC2) and specific PACAP (PAC1) receptors in human lung. Here we extend our aims to investigate by immunohistochemistry their localization and distribution at this level. A clear immunopositive reaction was obtained in human lung sections by using either anti-VPAC1 or -VPAC2 receptor antibodies but not with anti-PAC1 receptor antibody. However, PAC1 receptor (and VPAC1 and VPAC2 receptors) could be identified in lung membranes by immunoblotting which supports that the PAC1 receptor is expressed at a low density. Both VPAC1 and VPAC2 receptors showed similar immunohistochemical patterns appearing in smooth muscle cells in the wall of blood vessels and in white blood cells (mainly in areas with inflammatory responses). The results agree with previous evidence on the importance of both peptides in the immune system and support their anti-inflammatory and protective roles in lung.
Keywords: Vasoactive intestinal peptide; Pituitary adenylate cyclase-activating peptide; VPAC1 receptor; VPAC2 receptor; PAC1 receptor; Human lung;

Parallel increase in substance P and VIP in rat duodenum in response to irradiation by Ulf Höckerfelt; Lars Franzén; Uno Kjörell; Sture Forsgren (271-281).
Irradiation was administered to the upper abdomen of rats, whereupon the duodenum was examined. Numerous vasoactive intestinal peptide (VIP)- and substance P (SP)-like immunoreactive nerve fibers were seen in the damaged mucosa, often in close association to each other. The intensity of the SP- and VIP-like immunoreaction was increased in several of the tissue compartments and, as measured with radioimmunoassay, the contents of SP- and VIP-like materials were increased after 30 Gray. The results show that SP and VIP levels increase after irradiation and suggest that SP and VIP are involved in interactive reactions in the reorganization and inflammatory processes in the gut after abdominal irradiation.
Keywords: Vasoactive intestinal peptide; Substance P; Gastrointestinal tract; Radiotherapy; Radioimmunoassay; Immunohistochemistry;

Neural and muscular receptors for motilin in the rabbit colon by P Miller; L Trudel; S St-Pierre; H Takanashi; P Poitras (283-287).
Motilin receptors were classically recognized in the gastroduodenal area, where they help to regulate interdigestive motility. More recently, motilin receptors were identified in the colon where their biologic significance remains unclear. We aimed here to characterize the motilin receptors of the rabbit colon. Distal colon and duodenum were obtained from sacrificed rabbits. Tissues homogenized by Polytron were submitted to differential centrifugation to obtain neural synaptosomes or smooth muscle plasma membranes enriched solutions. Motilin binding to these membranes was determined by the displacement of 125I MOT by the native peptide MOT 1–22, or by peptide analogues MOT 1–12 [CH2NH]10–11 or GM-109 and by erythromycin derivative GM-611. Motilin binding capacity was maximum in colon nerves (49.5 ± 6.5 fmol/mg protein vs. 19.9 ± 2.5 in colon muscles or 9.4 ± 2.8 and 6.6 ± 1.2 in duodenal muscles and antral nerves respectively); all tissues expressed similar affinity for MOT 1–22, and the motilin agonist GM-611 bound equally to neural or muscle tissues from the rabbit colon; the synthetic antagonist MOT 1–12 [CH2NH]10–11 showed greater affinity for colon nerves than for colon muscles (plC50: 7.23 ± 0.07 vs. 6.75 ± 0.03). Similar results were obtained with the peptide antagonist GM-109; receptor affinity toward MOT 1–12 [CH2NH10–11] was always five times superior in neural tissues, whether they came from the colon or the antrum, than in muscle tissues, whether they were obtained from colon or from duodenum. Motilin receptors are found in very high concentration in nerves and in muscles from rabbit colon; specific motilin receptor subtypes are identified in nerves (N) and muscles (M) of the rabbit colon; N and M receptor subtypes seem independent of the organ location.
Keywords: Regulatory peptides; GI peptides; GI motility;

Valaminols, probably the most simplified peptide-analogs acting as pepsin inhibitors by Martin Kratzel; Andreas Bernkop–Schnürch (289-293).
Recently, we have introduced simplified analogs of pepstatin A, representing ‘tripeptides’ with two valine residues which are C-terminated by an amino alcohol moiety. In the present study, we have deleted one valine unit, yielding simple molecules—called ‘valaminols’—which can be prepared in big scale under really low costs. First investigations on structure-activity relationships revealed that the most active compound is a valaminol bearing both natural substituents either at the N-terminus or at the C-terminal side chain. Its inhibitory activity fully corresponds to the activity of tripeptides, hitherto reported by us, although one valine residue has been omitted.
Keywords: Pepstatin A; Enzyme inhibitors; Pepsin inhibition; Pepstatin analogs;

Inhibitory effect of intracerebroventricularly-administered [d-Arg2, β-Ala4]-dermorphin (1–4) on gastrointestinal transit by Fukie Niijima; Koichi Tan-No; Akihisa Esashi; Osamu Nakagawasai; Takeshi Tadano; Norio Takahashi; Akihiko Yonezawa; Shinobu Sakurada; Kensuke Kisara (295-299).
The inhibitory effect of intracerebroventricularly-administered [d-Arg2, β-Ala4]-dermorphin (1–4) (TAPA), a highly selective μ1-opioid receptor agonist, on mouse gastrointestinal transit was compared with that of morphine and [d-Ala2, N-methyl-Phe4, Gly5-ol]-enkephalin (DAMGO). When administered intracerebroventricularly 5 min before the oral injection of charcoal meal, TAPA (10–100 pmol), morphine (0.25–4 nmol), and DAMGO (20–80 pmol) dose-dependently inhibited gastrointestinal transit of charcoal. The inhibitory effect of each μ-opioid receptor agonist was completely antagonized by naloxone, a nonselective opioid receptor antagonist. The inhibitory effects of morphine and DAMGO were significantly antagonized by both β-funaltrexamine, a selective μ-opioid receptor antagonist, and naloxonazine, a selective μ1-opioid receptor antagonist. In contrast, the inhibitory effect of TAPA was not affected at all by β-funaltrexamine, naloxonazine, nor-binaltorphimine (a selective κ-opioid receptor antagonist), or naltrindole (a selective δ-opioid receptor antagonist). These results suggest that the inhibitory effect of TAPA on gastrointestinal transit may be mediated through an opioid receptor mechanism different from that of morphine and DAMGO.
Keywords: Dermorphin analog; Morphine; [d-Ala2; N-methyl-Phe4; Gly5-ol]-enkephalin; Gastrointestinal transit; Mouse;

Acute treatment of rats with haloperidol results in a rapid and transient increase in striatal c-fos mRNA and Fos immunoreactivity. The induction of immediate early genes by haloperidol may be involved in the development of extrapyramidal side effects. l-Prolyl-l-leucyl-glycinamide (PLG, or MIF-1) has been observed to antagonize the development of haloperidol-induced D2 receptor supersensitivity in rats. We investigated the modulatory effects of PLG on haloperidol-induced c-fos and Fos protein expression in the rat striatum. We report that coadministration of either PLG or the potent analog of PLG, 3(R)-[(2(S)-pyrrolidylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA), attenuated haloperidol-induced c-fos and Fos expression. Haloperidol induced [2 mg/kg, intraperitoneally (i.p.)] c-fos and Fos expression by 500% and 100%, respectively. These responses were attenuated by 170% and 75%, respectively, when coadministered with PLG (20 mg/kg, i.p.) or by 79% by PAOPA (10 μg/kg, i.p.).
Keywords: Striatum; Neuroleptics; Immediate-early genes; PLG; Dopamine; c-fos;

Secretin, glucagon, gastric inhibitory polypeptide (GIP), and parathyroid hormone (PTH) belong, together with vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase (AC)-activating polypeptide, to a family of peptides (the VIP-secretin-glucagon family), which also includes growth hormone-releasing hormone and exendins. All the members of this peptide family possess a remarkable amino-acid sequence homology, and bind to G-protein-coupled receptors, whose signaling mechanism primarily involves AC/protein kinase A and phospholipase C/protein kinase C cascades. VIP and pituitary AC-activating polypeptide play a role in the regulation of the hypothalamus–pituitary–adrenal (HPA) axis, and in this review we survey findings that also other members of the VIP-secretin-glucagon family may have the same function. Secretin and secretin receptors are expressed in the hypothalamus and pituitary gland, and secretin inhibits adrenocorticotropic hormone (ACTH) release. No evidence is available for the presence of secretin receptors in adrenal glands, but secretin selectively depresses the glucocorticoid response to ACTH of dispersed zona fasciculata-reticularis (ZF/R) cells. Glucagon and glucagon-like peptide-1 are contained in the hypothalamus, and all the components of the HPA axis are provided with glucagon and glucagons-like-1 receptors. These peptides exert a short-term inhibitory effect on stress-induced pituitary ACTH release and depress the ZF/R cell response to ACTH by inhibiting the AC/protein kinase A cascade; they also stimulate hypothalamic arginine-vasopressin release. GIP receptors are present in the ZF/R of the normal adrenals, and are particularly abundant in some types of adrenocortical adenomas and hyperplasias. GIP, through the activation of the AC/protein kinase A cascade, evokes a sizeable glucocorticoid secretagogue effect, leading to the identification of a food/GIP-dependent Cushing’s syndrome. PTH and PTH-related protein are expressed in the hypothalamus and pituitary gland, and PTH and PTH-related protein receptors in all the components of the HPA axis. Both peptides enhance ACTH and arginine-vasopressin release, as well as stimulate aldosterone and glucocorticoid secretion of dispersed zona glomerulosa and ZF/R cells, respectively. The involvement of growth hormone-releasing hormone and exendins in the functional regulation of the HPA axis has not yet been extensively investigated.
Keywords: Secretin; Glucagon; Gastric inhibitory polypeptide; Parathyroid hormone; Hypothalamus–pituitary–adrenal axis; Adrenal gland; Steroid secretion;