Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary adenylate cyclase activating polypeptide 38 (PACAP 38) and its fragments PACAP 27, PACAP 16-38, PACAP 28-38, PACAP 31-38 were compared for their histamine releasing effects on rat peritoneal mast cells. PACAP 38 and PACAP 16-38 were the most active peptides, followed by PACAP 27. PACAP 38 and PACAP 16-38 dose-dependently increased histamine release at a concentration of 1 x 10(-8) mol/l or higher, and these releasing activities were more than 100 times more potent than that of substance P. Extracellular calcium inhibited the substance P-induced histamine release. In contrast, PACAP 38- and PACAP 27-induced histamine releases were hardly inhibited by extracellular calcium.
 ...
PMID:Histamine release induced by pituitary adenylate cyclase activating polypeptide from rat peritoneal mast cells. 752 12

1. In the presence of atropine (1 microM), guanethidine (3 microM), indomethacin (3 microM), nifedipine (1 microM), L-nitroarginine (L-NOARG, 100 microM), and the selective tachykinin NK1 and NK2 receptor antagonists, SR 140,333 and GR 94,800, respectively (0.1 microM each), a single pulse of electrical field stimulation (EFS) produced a monophasic non-adrenergic non-cholinergic (NANC) inhibitory junction potential (i.j.p., about 10 mV in amplitude) in the circular muscle of guinea-pig proximal colon, recorded by the modified single sucrose gap technique. 2. The P2 purinoceptor agonist, alpha, beta methylene ATP (alpha, beta mATP, 100 microM) and the pituitary adenylyl cyclase activating peptide (PACAP, 1 microM) both produced hyperpolarization (11 +/- 0.8 mV, n = 14 and 10.2 +/- 0.8 mV, n = 19, respectively) and relaxation (1.1 +/- 0.2 mV, n = 14 and 1.5 +/- 0.2 mN, n = 19, respectively) of the circular muscle. 3. Apamin (0.1 microM) nearly abolished (about 90% inhibition) the NANC i.j.p. and the alpha, beta mATP-induced hyperpolarization, markedly reduced the alpha, beta mATP-induced relaxation (73% inhibition) and the PACAP-induced hyperpolarization (65% inhibition), while the PACAP-induced relaxation was unaffected. 4. Tetraethylammonium (TEA, 10 mM) increased the EFS-evoked i.j.p. and revealed an excitatory junction potential (e.j.p.). In the presence of TEA, alpha, beta mATP induced a biphasic response: transient depolarization and contraction followed by hyperpolarization and relaxation. The hyperpolarization to PACAP was reduced by TEA (45% inhibition) but the relaxation was unaffected. 5. The combined application of apamin (0.1 microM) and TEA (10 mM) abolished the i.j.p. and single pulse EFS evoked a pure e.j.p. with latency three times longer than that of the i.j.p. In the majority of strips tested, alpha, beta mATP and PACAP elicited a biphasic response : depolarization and small contraction followed by hyperpolarization and relaxation. 6. The P2 purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) inhibited the NANC i.j.p. in concentration-dependent manner and inhibited the alpha, beta mATP-induced hyperpolarization and relaxation, without affecting the hyperpolarization and relaxation induced by PACAP. On the other hand, the P2 purinoceptor antagonist, suramin (100 microM) inhibited to a similar extent (60-80%) the NANC i.j.p. and the hyperpolarization and relaxation induced by alpha, beta mATP or PACAP. 7. PPADS and suramin reduced the NANC e.j.p. evoked by a single pulse EFS in the presence of apamin and TEA (100 microM of PPADS and 300 microM of suramin inhibited the e.j.p. by about 40%). 8. We conclude that ATP, but not PACAP, mediates the apamin-sensitive NANC i.j.p. in the circular muscle of the guinea-pig colon. After blockade of the NANC i.j.p., ATP may act as an excitatory transmitter by activating excitatory P2 purinoceptors. The subtypes of P2 purinoceptor involved in the inhibitory and excitatory responses remain to be established. The data suggest that excitatory P2 purinoceptors may be located extrajunctionally.
 ...
PMID:The possible role of ATP and PACAP as mediators of apaminsensitive NANC inhibitory junction potentials in circular muscle of guinea-pig colon. 892 21

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.
 ...
PMID:Neuropeptides in idiopathic chronic constipation (slow transit constipation). 934 69

The ability of neuropeptides to modulate enteric smooth muscle proliferation was examined in primary explant cultures of rabbit gastric antrum and colon smooth muscle. Cell proliferation was determined by [3H]thymidine incorporation measurements and cell counting. Subcultured rabbit antrum and colon myocytes (passages 2-6) preserved a smooth muscle phenotype, as verified by immunohistochemistry for alpha-smooth muscle actin and electron microscopy. Both vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide-(1-38) [PACAP-(1-38)] concentration dependently (10(-10) to 10(-6) M) inhibited the serum-induced [3H]thymidine incorporation [in colon, 48.2 +/- 5.8 and 55.6 +/- 9.3% of control with 10(-6) M VIP and 10(-7) M PACAP-(1-38)] and inhibited increase in cell numbers in cultures derived from the colon but not in those from the antrum. Effects of VIP and PACAP-(1-38) were mimicked by forskolin (10(-7) to 10(-6) M) but not by 8-bromo-cGMP, whereas theophylline enhanced the effects of VIP. Inhibition of nitric oxide synthase with NG-nitro-L-arginine methyl ester (10(-3.5) M) did not alter the effects of VIP. Substance P, motilin, calcitonin gene-related peptide, and somatostatin had no effect. A single class of 125I-labeled VIP binding sites was found in antrum and colon myocyte cultures with an equal affinity for VIP and PACAP-(1-38) [dissociation constant (Kd) in antrum = 3.4 +/- 0.8 nM for VIP and 2.0 +/- 1.0 nM for PACAP-(1-38); Kd in colon = 2.0 +/- 1.0 nM for VIP and 2.8 +/- 1.6 nM for PACAP-(1-38)]. Density of binding sites in the antrum was higher than in the colon. In disease states such as inflammatory bowel disease, inhibition of myocyte proliferation by VIP and PACAP may serve to control smooth muscle hyperplasia in the colon but not in the antrum.
 ...
PMID:Region-specific antiproliferative effect of VIP and PACAP-(1-38) on rabbit enteric smooth muscle. 988 8

In summary, PACAP exerts a biphasic effect (an initial contraction followed by a relaxation) in the IAS. The initial contractile effect with higher concentrations of PACAP was found to be mediated by the activation of PACAP receptor at the substance P-containing nerve terminals. The PACAP receptor(s) responsible for the inhibitory action of the neuropeptide is(are) hypothesized to be present in the IAS smooth muscle cells and on the myenteric nerve terminals. The exact nature and the role of PACAP and the PACAP receptors in the inhibitory neurotransmission, the relationship of PACAP receptors with substance P-containing neurons and IAS smooth muscle cells, and interactions with the NOS pathway and VIP remain to be determined.
 ...
PMID:Sites of actions of contractile and relaxant effects of pituitary adenylate cyclase activating peptide (PACAP) in the internal anal sphincter smooth muscle. 992 59

The data obtained suggest a potential mechanism that may account for the selective control of adrenaline and noradrenaline release from adrenal chromaffin cells. Some neuropeptides seem to affect in a different way the release from A- and NA-adrenal cells by means of regulating a set of cytochemical events: specific reception of cholinergic transmitters, expression of the second messenger system including cGMP and changes in Ca channels activity, changes in the catecholamine biosynthesis in adrenal chromaffin cells. Modulating function of substance P, endothelins, PACAP, and ANF, is discussed.
 ...
PMID:[Peptide mediators in adrenal chromaffin cells: regulation of catecholamine selective secretion]. 1009 82

Peptides involved in the endocrine and enteric nervous systems as well as in the central nervous system exert concerted action on gastrointestinal motility. Mechanical and chemical stimuli which induce peptide release from the epithelial endocrine cells are the earliest step in the initiation of peristaltic activities. Gut peptides exert hormonal effects, but peptide-containing stimulatory (Ach/substance P/tachykinin) and inhibitory (VIP/PACAP/NO) neurons are also involved in the induction of ascending contraction and descending relaxation, respectively. The dorsal vagal complex (DVC), located in the medulla of the brainstem, constitutes the basic neural circuitry of vago-vagal reflex control of gastrointestinal motility. Several gut peptides act on the DVC to modify vagal cholinergic reflexes directly (PYY and PP) or indirectly via afferent fibers in the periphery (CCK and GLP-1). The DVC is also a primary site of action of many neuropeptides (such as TRH and NPY) in mediating gastrointestinal motor activities. The identification over the last few years of a number of neuropeptide systems has greatly changed the field of feeding and body weight regulation. By exploring the brain and gut systems that employ recently identified peptidergic molecules, it will be possible to elaborate on the central and peripheral pathways involved in the regulation of gastrointestinal motility.
 ...
PMID:Peptidergic regulation of gastrointestinal motility in rodents. 1106 6

Adrenocortical steroidogenesis is regulated in addition to a central regulation via the hypothalamus-pituitary-adrenal axis by intra-adrenal mechanisms involving the adrenal medulla. We could previously show that adrenocortical steroidogenesis is stimulated by co-culturing bovine adrenocortical cells with medullary chromaffin cells. This stimulation was due to soluble factors released from the chromaffin cells under basal, unstimulated conditions and involved the increased expression of P450 enzymes, StAR and de novo protein synthesis. In the present study we analyzed the differential regulation of the three cortical zones and characterized secretagogues involved in this stimulation. While cortisol and androstenedione release were increased 10 fold by incubation with chromaffin cell-conditioned medium, aldosterone secretion was not influenced. 80% of the stimulation proved to be due to adrenomedullary epinephrine, norepinephrine, ACTH, PACAP and PG-dependent mechanisms. Other adrenomedullary secretory products, serotonin, Met-enkephalin, Leu-enkephalin, galanin, CGRP, substance P, VIP or NPY did not stimulate steroidogenesis in this system. Our data show that adrenomedullary cells differentially regulate the three adrenocortical zones. This stimulation predominantly depended on epinephrine, norepinephrine, PACAP, and ACTH released from the chromaffin cells and prostaglandin-dependent mechanisms such as interleukin-1.
 ...
PMID:Neurotransmitters and neuropeptides in the differential regulation of steroidogenesis in adrenocortical-chromaffin co-cultures. 1119 60

Gut motility in non-mammalian vertebrates as in mammals is controlled by the presence of food, by autonomic nerves and by hormones. Feeding and the presence of food initiates contractions of the stomach wall and subsequently gastric emptying, peristalsis, migrating motor complexes and other patterns of motility follow. This overview will give examples of similarities and differences in control systems between species. Gastric receptive relaxation occurs in fish and is an enteric reflex. Cholecystokinin reduces the rate of gastric emptying in fish as in mammals. Inhibitory control of peristalsis is exerted, e.g. by VIP, PACAP, NO in fish and amphibians, while excitatory stimuli arise from nerves releasing tachykinins, acetylcholine or serotonin (5-HT). In crocodiles, we have found the presence of the same nerve types, although the effects on peristalsis have not been studied. Recent studies on signal transduction in the gut smooth muscle of fish and amphibians suggest that external Ca2+ is of great importance, but not the only source of Ca2+ recruitment in tachykinin-, acetylcholine- or serotonin-induced contractions of rainbow trout and Xenopus gastrointestinal smooth muscle. The effect of acetylcholine involves reduction of cAMP-levels in the smooth muscle cells. It is concluded that, in general, the control systems in non-mammalian vertebrates are amazingly similar between species and animal groups and in comparison with mammals.
 ...
PMID:The control of gut motility. 1124 40

Substance P (SP) and calcitonin gene-related peptide (CGRP), released from capsaicin-sensitive sensory nerves induce local neurogenic inflammation, while somatostatin exerts systemic anti-inflammatory actions. The aim of the present study was to investigate the release of pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) and its effects on sensory neuropeptide release in vitro and acute neurogenic ear swelling in vivo. Capsaicin (10(-6) M) or electrical field stimulation (EFS; 40 V, 0.1 ms, 10 Hz, 120 s; 1200 impulses)-induced release of PACAP-38, SP, CGRP and somatostatin from isolated rat tracheae was measured with radioimmunoassay. Mustard oil-induced neurogenic inflammation in the mouse ear was determined with a micrometer and in the rat hind paw skin by the Evans Blue leakage technique. Capsaicin and EFS evoked 27% and more than twofold elevation of PACAP-38 release respectively, compared with the prestimulated basal values from isolated trachea preparation. Exogenously administered PACAP-38 (20-2000 nM) diminished both capsaicin- and EFS-evoked sensory neuropeptide release in a concentration-dependent manner. The maximal inhibitory effects of PACAP on capsaicin-induced substance P, CGRP and somatostatin release amounted to 75.4%, 73.3% and 90.0%, while EFS-evoked release of these peptides was 80.03%, 87.7% and 67.7%. In case of capsaicin stimulation the EC50 values for substance P, CGRP and somatostatin were 82.9 nM, 60.1 nM and 66.9 nM, respectively. When EFS was performed, these corresponding EC50 data were 92.1 nM, 67.8 nM and 20.9 nM. PACAP-38 (10, 100 and 1000 microg/kg i.p. in 200 microl volume) inhibited neurogenic ear swelling in the mouse. Furthermore, 100 microg/kg i.p. PACAP also significantly diminished mustard oil-evoked plasma protein extravasation in the rat skin. These results suggest that PACAP-38 is released from the stimulated peripheral terminals of capsaicin-sensitive afferents and it is able to inhibit the outflow of sensory neuropeptides. Based on this mechanism of action PACAP is also able to effectively diminish/abolish neurogenic inflammatory response in vivo after systemic administration.
 ...
PMID:Effect of pituitary adenylate cyclase activating polypeptide-38 on sensory neuropeptide release and neurogenic inflammation in rats and mice. 1693 9


1 2 Next >>