Peptides (v.23, #9)

Characterization of antimalarial SPf66 peptide using MALDI–TOF MS, CD and SEC by Alexis Oliva; Maria Jesús Dorta; Ana Santoveña; Valentina Bonetto; Mario Salmona; José B. Fariña (1527-1535).
SPf66 is the first chemically synthesized peptide to elicit a partial protective immune response against malaria. Size-exclusion chromatography (SEC) with multi-angle laser light-scattering (MALLS) detection and hydrogen/deuterium (H/D) exchange monitored by (matrix-assisted laser desorption/ionization) MALDI–TOF (time-of-flight) mass spectrometry (MS) were used to assess the conformation and stability in aqueous solution after storage at different temperatures. Moreover, the feasible conformational changes of this peptide were also measured by circular dichroism (CD)-spectroscopy. The absolute molecular weight of SPf66 monomer and dimer species were 4765 and 8960 Da using SEC with MALLS detection, and 4643 and 9490 Da by MALDI–TOF MS, the discrepancy being between both methods lower than 5.7%, a value quite close to those found in other proteins. The results from H/D exchange monitored by MALDI–TOF MS and CD-spectroscopy show that the SPf66 monomer lacks ordered structure, whereas the SPf66 dimer species presents segments of secondary structure as a determined by CD measurements.
Keywords: SPf66 peptide; MALDI–TOF MS; SEC; Circular dichroism; Multi-angle laser light-scattering; Secondary structure; Molecular mass;

Significance of a carboxyl-terminal amide moiety in the folding and biological activity of crustacean hyperglycemic hormone by Hidekazu Katayama; Tsuyoshi Ohira; Katsumi Aida; Hiromichi Nagasawa (1537-1546).
Recombinant peptides related to Pej-SGP-I, one of several crustacean hyperglycemic hormones (CHHs) existing in the kuruma prawn Penaeus japonicus, were expressed in bacterial cells, and then purified after being allowed to refold. Their circular dichroism spectra suggested that the recombinant Pej-SGP-I having a free carboxyl-terminus (rPej-SGP-I-OH) differed slightly in secondary structure from the recombinant Pej-SGP-I having an amidated C-terminus (rPej-SGP-I-amide). The hyperglycemic activity of rPej-SGP-I-amide was comparable to that of natural Pej-SGP-I, whereas rPej-SGP-I-OH showed weaker hyperglycemic activity by approximately one order of magnitude. These results indicate that the C-terminal amide of CHH affects secondary structure and is significant in conferring hyperglycemic activity.
Keywords: Carboxyl-terminal amide; Circular dichroism spectrum; Crustacean hyperglycemic hormone; Kuruma prawn; Penaeus japonicus; Secondary structure;

Bradykinins and their precursor cDNAs from the skin of the fire-bellied toad (Bombina orientalis) by Tianbao Chen; David F Orr; Anthony J Bjourson; Stephen McClean; Martin O’Rourke; David G Hirst; Pingfan Rao; Chris Shaw (1547-1555).
Bradykinin and (Thr6)-bradykinin have been identified in the defensive skin secretion of the fire-bellied toad, Bombina orientalis. The homologous cDNAs for both peptides were cloned from a skin library using a 3′- and 5′-RACE strategy. Kininogen-1 (BOK-1) contained an open-reading frame of 167 amino acid residues encoding four repeats of bradykinin, and kininogen-2 (BOK-2) contained an open-reading frame of 161 amino acid residues encoding two repeats of (Thr6)-bradykinin. Alignment of both precursor nucleotide and amino acid sequences revealed a high degree of structural similarity. These amphibian skin kininogens/preprobradykinins are not biologically analogous to mammalian kininogens.
Keywords: Amphibian; Skin; Peptides; Bradykinin; Mass spectrometry; Kininogen; Preprobradykinin; Cloning;

Peptide nucleic acid (PNA) sequences are synthetic versions of naturally ocurring oligonucleotides which display improved binding properties to DNA and RNA, but are still poorly internalized across cell membranes. In an effort to employ the rapid binding/internalization properties of somatostatin agonist analogs and the over-expression of somatostatin receptors on many types of tumor cells, PNAs complementary to target sites throughout 5′-UTR, translation start site and coding region of the n-myc oncogene were conjugated to a somatostatin analog (SSA) with retention of high somatostatin biological potency. IMR32 cells, which over-express somatostatin receptor type 2 (SSTR2) and contain the n-myc oncogene, were treated with these PNA–SSA conjugates. The results show that PNA conjugates targeted to the 5′-UTR terminus and to regions at or close to the translation start site could effectively inhibit n-myc gene expression and cell growth, whereas the non-conjugate PNAs were without effect at similar doses. The most potent inhibition of cell growth was achieved with PNAs binding to the translation start site, but those complementary to the middle coding region or middle upstream site between 5′-UTR and translation start site displayed no inhibition of gene expression. These observations were extended to four other cell lines: GH3 cells which express SSTRs with the n-myc gene, SKNSH cells containing a silent n-myc gene without SSTR2, HT-29 cells carrying the c-myc but no n-myc gene, and CHO-K1 cells lacking SSTR2 with n-myc gene. The results show that there was almost no effect on these four cell lines. Our study indicates that PNAs conjugated to SSA exhibited improved inhibition of gene expression possibly due to facilitated cellular uptake of the PNAs. These conjugates were mRNA sequence- and SSTR2-specific suggesting that many other genes associated with tumor growth could be targeted using this approach and that SSA could be a novel and effective transportation vector for the PNA antisense strategy.
Keywords: Somatostatin analog; Oncogene; n-myc; Peptide nucleic acid (PNA); Human neuroblastoma cell; IMR32; Somatostatin receptor;

Isolation of cathepsin B inhibitory peptides, Cabin-A1 and -A2, from a tryptic and chymotryptic hydrolysate of human serum albumin by Kazuya Nakagomi; Kouki Takatsu; Shinobu Takagi; Hidetoshi Ebisu; Yutaka Sadakane; Noriko Fujii; Toshifumi Akizawa; Takenori Tanimura; Yasumaru Hatanaka (1567-1571).
Two novel peptides that inhibit cathepsin B were isolated from a tryptic and chymotryptic hydrolysate of human serum albumin, and designated as Cabin-A1 and -A2. Cabin-A1 and -A2 were purified by reversed-phase HPLC and identified as Ser–Leu–His–Thr–Leu–Phe and Phe–Gln–Asn–Ala–Leu, respectively. These peptides correspond to f(65–70) and f(403–407) of human serum albumin. Human albutensin A (Ala–Phe–Lys–Ala–Trp–Ala–Val–Ala–Arg), which corresponds to f(210–218), was also isolated as a potent cathepsin B inhibitor. Synthetic Cabin-A1, -A2, and human albutensin A showed dose-dependent inhibition of cathepsin B, with K i values of 2.4, 290, and 3.8 μM, respectively.
Keywords: Cabin-A1; Cathepsin B inhibitory peptide; Tryptic and chymotryptic hydrolysate; Human serum albumin; Albutensin A;

In vitro quantitative study of the degradation of endomorphins by Csaba Tömböly; Antal Péter; Géza Tóth (1573-1580).
The catabolism of the endomorphins was investigated in detail. The endomorphins were degraded relatively slowly in the rat brain homogenate (t 1/2(endomorphin-1)=4.94 min; t 1/2(endomorphin-2)=3.81 min). The inhibition of metalloproteases and aminopeptidases stabilised the endomorphins to the greatest extent. The digestion of endomorphins tritiated specifically on Tyr1, Pro2 or Phe3 established also that only the aminopeptidase pathways were essential for inactivation of the endomorphins, and that the tetrapeptides were degraded by cleavage of the Pro2Trp3 or Pro2Phe3 bond. The end-products of the catabolism were amino acids; the fragments Tyr–ProOH and Pro–Trp–PheNH2 were present as intermediates. Metabolites produced by brain carboxypeptidases were not detected.
Keywords: Opioid; Peptide; Endomorphin; Metabolism; Half-life; HPLC; Tritium;

Does nociceptin play a role in pain disorders in man? by Hanne Mørk; Kristine Hommel; Rolf Uddman; Lars Edvinsson; Rigmor Jensen (1581-1587).
Nociceptin-immunoreactive cellbodies were detected in the human trigeminal ganglion, while no such fibers were identified in the temporal artery or in dermal tissue from the neck region. In four healthy subjects receiving nociceptin into the temporal muscle in an open labeled design no pain was detected. In 10 healthy subjects who received 200 pmol of nociceptin into tender non-dominant trapezius muscles in a placebo-controlled, randomized, balanced, and double-blinded design local tenderness increased (P=0.025) while no pain was noted. Thus, the action of nociceptin should be searched for in the trigeminal ganglion and/or in the central nervous system (CNS).
Keywords: Nociceptin; Myofascial pain; Myofascial tenderness; Intra-muscular injection; Human;

Lack of the nociceptin receptor does not affect acute or chronic nociception in mice by Rosalia Bertorelli; Elena Bastia; Francesca Citterio; Laura Corradini; Angelo Forlani; Ennio Ongini (1589-1596).
The peptide nociceptin/orphanin FQ (N/OFQ) and its receptor ORL-1, also designated opioid receptor 4 (OP4) are involved in the modulation of nociception. Using OP4-knockout mice, we have studied their response following opioid receptor stimulation and under neuropathic conditions.In vas deferens from wild-type and OP4-knockout mice, DAMGO (μ/OP3 agonist), deltorphine II (δ/OP1 agonist) and (−)-U-50488 (κ/OP2 agonist) induced similar concentration-dependent inhibition of electrically-evoked contractions. Naloxone and naltrindole (δ/OP1 antagonists) shifted the curves of DAMGO (pA2=8.6) and deltorphine II (pA2=10.2) to the right, in each group. In the hot-plate assay, N/OFQ (10 nmol per mouse, i.t.) increased baseline latencies two-fold in wild-type mice while morphine (10 mg/kg, s.c.), deltorphine II (10 nmol per mouse, i.c.v.) and dynorphin A (20 nmol per mouse, i.c.v.) increased hot-plate latencies by about four- to five-fold with no difference observed between wild-type and knockout mice. Furthermore, no change was evident in the development of the neuropathic condition due to chronic constriction injury (CCI) of the sciatic nerve, after both thermal and mechanical stimulation.Altogether these results suggest that the presence of OP4 receptor is not crucial for (1) the development of either acute or neuropathic nociceptive responses, and for (2) the regulation of full receptor-mediated responses to opioid agonists, even though compensatory mechanisms could not be excluded.
Keywords: Hot-plate test; Chronic constriction injury; Nociceptin/orphanin FQ; OP4-knockout mice; Opioid receptors; Vas deferens assay;

Different effects of methionine-enkephalin on paw edema in two inbred rat strains by Stanislava Stanojević; Jelena Radulović; Vesna Kovačević-Jovanović; Vesna Vujić; Mirjana Dimitrijević (1597-1605).
The effect of intraplantarly ( methionine-enkephalin (ME) on Concanavalin A (Con A)-induced paw edema in Dark Agouti (DA) and Albino Oxford (AO) rats was investigated. ME suppressed edema in DA rats, which was antagonized with naloxone (non-selective opioid receptor antagonist) and naltrindole (δ opioid receptors antagonist). Potentiating effect of ME in AO rats was blocked by naloxone, nor-binaltorphimine (κ opioid receptors antagonist) and β-funaltrexamine (μ opioid receptors antagonist). Dexamethasone suppressed edema in both rat strains. These findings suggest that strain-dependent differences in the effects of ME on inflammation in DA and AO rats could be related to diversity in opioid receptors expression in these strains.
Keywords: Methionine-enkephalin; Naloxone; Naltrindole; nor-Binaltorphimine; β-Funaltrexamine; Concanavalin A; δ, κ, μ Opioid receptors; Paw edema; Rat strain;

Cloning and characterization of murine neuromedin U receptors by Sandrine Funes; Joseph A Hedrick; Shijun Yang; LiXin Shan; Marvin Bayne; Frederick J Monsma; Eric L Gustafson (1607-1615).
Neuromedin U (NmU) is a neuropeptide involved in various physiological functions such as feeding behavior, muscle contractile activity, and regulation of intestinal ion transport. Recently, two human G protein-coupled receptors have been identified as NmU-specific receptors, NmU-R1 and NmU-R2, which share 55% amino acid identity. It is unclear however, which of the two receptors mediates responses to NmU observed in rodent models. Attempts to define the pharmacological profile of the two receptors are confounded by overlapping expression of the two receptors and a lack of subtype-selective compounds. In order to establish a basis to further our understanding of the function of these receptors, we cloned and characterized the mouse homologues of the two human NmU receptors. Mouse NmU-R1 and mouse NmU-R2 are 79 and 81% identical to their respective human homologues. Expression of NmU-R1 was mainly observed in testis, gastrointestinal (GI) tract, and immune system, while NmU-R2 was primarily expressed in brain tissues. Each mouse receptor was independently expressed in HEK293 cells and demonstrated a dose-dependent calcium flux in response to NmU-8, NmU-23 and NmU-25. In an attempt to identify a synthetic NmU peptide that would exhibit selectivity at one of the two receptors, we examined the functional activity of eight alanine-substituted NmU-8 peptides. These experiments demonstrated that alanine substitution at positions 5 and 7 affects the functional activity of the peptide at both receptors. The arginine residue at position 7 is required for NmU-8 activity at either receptor while alanine substitution at position 5 selectively affects the potency and the efficacy at mNmU-R1. These experiments validate the use of rodent models to characterize NmU function relative to humans and suggest that substitution at Arginine-5 of NmU-8 may provide a receptor selective peptide.
Keywords: GPCR; Neuromedin U; NmU-R1; NmU-R2; Structure–activity relationship; Neuropeptide;

Developmental pattern of tachykinins during aging in several organs: effect of exogenous melatonin by C Fernández Alvarez; L Debeljuk; E Dı́az Rodrı́guez; B Dı́az López (1617-1623).
Mammalian neurokinin A (NKA) and substance P (SP) are neuropeptides widely distributed in the body; they are potential regulators of the basal blood flow and therefore of the function of many organs and tissues. In the present investigation, we studied the age-dependent changes in NKA and SP in ovary, liver, pancreas and spleen as well as the role of exogenous melatonin on these changes. Female rats of 5, 15 or 25 months of age were studied. In the ovary, NKA concentrations did not change during aging. SP concentrations in the control group were significantly higher (P<0.01) in old rats than in the other two age groups studied. Melatonin treatment resulted in reduced concentrations as compared with those of the control old rats. In the pancreas, NKA and SP concentrations increased during aging, the young rats showing significantly lower values (P<0.01) than middle-aged and old rats for NKA and significantly lower (P<0.01) than the old rats for SP. After melatonin treatment the differences in NKA concentrations disappeared and SP decreased in middle-aged as compared with those in old rats. In the liver, NKA and SP concentrations in the control and melatonin-treated groups did not differ significantly for the three age groups studied. Splenic NKA in control and melatonin-treated groups increased from young to middle-age up to old ages. SP concentrations showed similar values at all ages except in melatonin-treated old rats; in these animals there were significantly higher concentrations than in young melatonin-treated rats. The effect of melatonin was mainly observed on the ovary and pancreas in old rats, with a reduction in the concentrations as compared with those observed in the young groups.
Keywords: NKA; SP; Aging; Melatonin; Ovary; Pancreas; Liver; Spleen;

Alpha melanocyte stimulating hormone (αMSH) has been demonstrated to have regulatory functions in the periphery and central nervous system (CNS). αMSH plays a central role in the regulation of metabolic balance such as decreasing food intake, increasing sympathetic outflow and hypothalamic/pituitary function. Our laboratory has investigated the actions of αMSH on sympathetic and cardiovascular dynamics using anesthetized animals. In this study we determined both the acute and chronic effects of αMSH on cardiovascular and metabolic dynamics in conscious unrestrained rats. Animals were each implanted with a radio-telemetry transmitter for recording of cardiovascular parameters and subsequently instrumented with intracerebroventricular (ICV) cannulas. The acute ICV administration of αMSH significantly increased the mean arterial pressure (MAP) and heart rate (HR) when compared to artificial cerebrospinal fluid (ACSF) controls. On the other hand chronic αMSH infusion resulted in an initial increase in MAP and HR lasting for 2 days followed by a decrease in MAP. Chronic αMSH administration decreased physical activity and food intake but not weight gain. We conclude that in the conscious unrestrained animal the acute administration of αMSH increased MAP and HR, however, chronic infusion is associated with decreased MAP, physical activity and food intake.
Keywords: Alpha melanocyte stimulating hormone; Blood pressure; Heart rate; Activity; POMC products;

Cardiovascular effects of urotensin II in different brain areas by Yang Lu; Chang-Jiang Zou; Da-Wei Huang; Chao-Shu Tang (1631-1635).
It has been shown that intracerebroventricular injection of urotensin II (UII)-induced hypotensive and bradycardiac responses. Here, we tested the cardiovascular roles of UII in different brain areas by microinjection of UII into the A1 and A2 areas (noradrenergic cells found in the lower part of the medulla that have been designated either A1 or A2 areas), the paraventricular and the arcuate nucleus. In urethane-anaesthetized rats, we observed that: (1) microinjection of UII into the A1 area induced dose-related depressor and bradycardiac responses; (2) mean arterial blood pressure (mABP) and heart rate (HR) did not change significantly after microinjection of UII into the A2 area; and (3) significant increases in mABP and HR were induced after microinjection of 10 pmol UII into either the paraventricular or arcuate nucleus. The above results suggest that UII, in different brain areas, plays different roles in cardiovascular regulation and the A1 area is a very important action site for UII in cardiovascular regulation.
Keywords: Urotensin II; A1 area; A2 area; Paraventricular nucleus; Arcuate nucleus;

A-type natriuretic peptide receptor in the spontaneously hypertensive rat kidney by Geoffrey E Woodard; Jing Zhao; Juan A Rosado; John Brown (1637-1647).
Renal NPR-A binding characteristics was examined in SHR. Renal ANP binding sites of NPR-A showed a lower maximal binding capacity and higher affinity in SHR than in WKY at all intrarenal sites. Despite the lower B max in SHR, both ANP1–28 and ANP5–25 stimulate similar or greater cGMP production in isolated glomeruli. Studies on guanylate cyclase from glomerular and papillary membranes have reported an increased basal and stimulated guanylate cyclase activity in SHR. The present study provides further evidences for altered NPR-A receptors in SHR kidney, which might act as a negative feedback in response to hypertension.
Keywords: ANP; NPR-A; Hypertension; Kidney;

GRP mediates an inhibitory response of gut-related vagal motor neurons to PVN stimulation by Xueguo Zhang; Xiankui Sun; William E Renehan; Ronald Fogel (1649-1661).
We previously characterized neurons in the dorsal motor nucleus of the vagus (DMNV) that were modulated by electrical stimulation of the PVN and by gastrointestinal distention. Bombesin has been identified in a subset of PVN neurons projecting to the DMNV. It is currently unknown whether this neurotransmitter is involved in descending communication from PVN to DMNV neurons. In this study we determined whether the specific bombesin antagonist, N-acetyl-GRP20–26, influenced (1) the basal firing rate of DMNV neurons and (2) the response to electrical current stimulation of the PVN. Our results indicate that N-acetyl-GRP20–26, significantly attenuated the inhibitory response of DMNV neurons to PVN stimulation. These results provide a possible mechanism by which bombesin regulates gastrointestinal function, body temperature homeostasis, and feeding behaviors.

α2-Adrenoceptors control the release of noradrenaline but not neuropeptide Y from perivascular nerve terminals by M.Verónica Donoso; Andrés Carvajal; Alfonso Paredes; Alexander Tomic; Cecilia S Koenig; J.Pablo Huidobro-Toro (1663-1671).
Neuropeptide Y (NPY) and noradrenaline (NA) are co-transmitters at many sympathetic synapses, but it is not yet clear if their release is independently regulated. To address this question, we quantified the electrically evoked release of these co-transmitters from perivascular nerve terminals to the mesenteric circulation in control and drug-treated rats. 6-Hydroxydopamine reduced the tissue content and the electrically evoked release of ir-NPY and NA as well as the rise in perfusion pressure. A 0.001 mg/kg reserpine reduced the content of ir-NPY and NA, but did not modify their release nor altered the rise in perfusion pressure elicited by the electrical stimuli. However, 0.1 mg/kg reserpine reduced both the content and release of NA but decreased only the content but not the release of ir-NPY; the rise in perfusion pressure was halved. Clonidine did not affect the release of ir-NPY while it lowered the outflow of NA, not altering the rise in perfusion pressure elicited by the electrical stimuli. Yohimbine, did not modify the release of ir-NPY but increased the NA outflow, it antagonized the clonidine effect. Therefore, presynaptic α2-adrenoceptors modulate the release of NA but not NPY, implying separate regulatory mechanisms.

Although orexin was found to promote food intake, recent reports proposed its involvement in the regulation of vigilance. To study the mechanism of how orexin affects arousal, we analyzed glutamate (GLU) release from the locus coeruleus (LC) in rats after systemic injection of orexin-A. Baseline levels of orexin-A in the LC were significantly higher during the dark period than the light period. Intravenous administration of orexin-A increased GLU levels as well as orexin in the LC, simultaneously promoting wakefulness. These results suggest that increases in GLU release may reflect the arousal-inducing effects of orexin.
Keywords: Orexin-A; Diurnal variation; Glutamate (GLU); CSF; Microdialysis; Locus coeruleus; Hypocretin;

Effects of orexin-A on memory processing by Laura B Jaeger; Susan A Farr; William A Banks; John E Morley (1683-1688).
Orexin-A is an endogenous peptide with receptors present throughout the brain. Here, we examined the effect of post-training administration of orexin-A on retention in active and passive avoidance. Orexin-A administered by intracerebroventricular (i.c.v.) injection to CD-1 mice post-training improved retention in both T-maze footshock avoidance and one trial step-down passive avoidance. SAMP8 mice have age-related deficits in learning and memory, which correlate with an increase in brain levels of beta amyloid (Aβ) and an impaired response to memory-enhancing compounds. Orexin-A at 3 nmol improved retention in young and old SAMP8 mice. These findings show that orexin-A can improve memory even with overproduction of Aβ.

Expressions of the prepro-orexin and orexin type 2 receptor genes in obese rat by Yukiyo Yamamoto; Yoichi Ueta; Hiroshi Yamashita; Kohtaro Asayama; Akira Shirahata (1689-1696).
We examined the expressions of the prepro-orexin gene in the lateral hypothalamic area (LHA), the genes of the neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the arcuate nucleus (ARC), the orexin type 1 receptor (OX1R) gene in the ventromedial hypothalamic nucleus (VMH) and the orexin type 2 receptor (OX2R) gene in the paraventricular nucleus (PVN) in 6-, 12- and 18-week-old male lean (Fa/?) and obese (fa/fa) Zucker rats, using in situ hybridization histochemistry. The fa/fa rats showed hyperglycemia at 12- and 18-week-old. The prepro-orexin mRNA level in fa/fa rats at 18-week-old and the OX2R mRNA level in fa/fa rats at 12- and 18-week-old were significantly decreased compared to controls. The NPY mRNA levels in fa/fa rats at each time point were significantly increased compared to controls, but the POMC mRNA levels were decreased. Prepro-orexin and OX2R mRNA levels in fa/fa rats pretreated with insulin normalized to the levels found in Fa/? rats. These results suggest that the regulation of prepro-orexin gene expression might be independent of the regulation of the NPY and POMC genes in the ARC in fa/fa rats.
Keywords: fa/fa; Hypothalamus; Hypocretin; In situ hybridization histochemistry; Orexin; Orexin receptors;

The involvement of the hypothalamic melanocortin-3 and -4 (MC3/4) receptors system in the inhibitory actions of estradiol (E2) on feeding was investigated. Ovariectomized Long–Evans rats with lateral ventricular (LICV) injection cannulae were maintained on a near-physiological, cyclic schedule of E2 treatment. LICV injections of 0.5 nmol of the MC3/4 agonist MTII decreased feeding, and LICV injections of the MC3/4 antagonists SHU9119 (12.5–500 pmol) and AgRP (1.0 nmol) stimulated feeding. None of these effects was affected by E2 treatment. Thus, hypothalamic MC3/4 receptors play a physiological role in the control of feeding in female rats as in males but do not mediate E2’s feeding effects during the ovarian cycle.
Keywords: Meal size; Satiation; Sex differences; Ovarian hormones; Anorexia; α-Melanin-stimulating hormone (α-MSH); Agouti-related peptide (AgRP);

Peptides acting at gap junctions by Stefan Dhein (1701-1709).
Gap junction channels are low resistance pathways allowing an action potential to propagate from one cell to the neighboring. Moreover, small molecules (<1000 Da) may pass the channel providing a possibility for metabolic coupling, growth and differentiation control of a cell by its surrounding. Antiarrhythmic peptides can enhance the conductivity of the channels while other peptides, angiotensin or extracellular loop peptides, reduce intercellular communication. On the other hand, peptides like angiotensin II or endothelin-1 can increase expression of certain gap junction channel proteins and, thereby, may affect intercellular coupling chronically. Thus, intercellular communication can be controlled using peptide drugs.
Keywords: Gap junction; Connexin; Antiarrhythmic peptide; Endothelin; Angiotensin; Extracellular loop peptide;