Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on growth hormone (GH) release was compared with that of prostaglandin E2 (PGE2) and growth hormone releasing factor (GRF) from cultured bovine anterior pituitary cells in vitro. Both PACAP and PGE2 stimulated GH release at concentrations as low as 10(-9) and 10(-8) M, respectively, (P < 0.01). However, GRF released GH at a concentration as low as 10(-13) M (P < 0.01). Percent increases of GH compared with controls were not significantly different among GRF, PACAP, and PGE2 at 10(-7) M; however, the increases of GH by the 10(-8) M GRF, PACAP and PGE2 were 196, 118, and 27%, respectively, (P < 0.01), and 124, 65, and 1% in the 10(-9) M media, respectively, (P < 0.01). When GRF and somatostatin (SS) were added together, the GH releasing effect of GRF was blunted (P < 0.01). Similar bluntness were observed in PACAP and PGE2, when SS was added. The stimulatory effects of GRF and PGE2 together were similar to that by either GRF or PGE2 alone. When GRF and PACAP were added together, the GH released by both secretagogues was greater than that by PACAP alone (P < 0.01); however, a synergistic effect was not clear when compared with GRF alone. These findings suggest that PACAP and PGE2 may modulate the release of GH in cattle.
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PMID:Effects of pituitary adenylate cyclase-activating polypeptide (PACAP), prostaglandin E2 (PGE2) and growth hormone releasing factor (GRF) on the release of growth hormone from cultured bovine anterior pituitary cells in vitro. 782 27

Somatostatin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been originally isolated from the ovine hypothalamus on the basis of their hypophysiotropic activities. There is now evidence that somatostatin and PACAP may play a role in the development of the central nervous system, particularly in the cerebellum. High concentrations of somatostatin and somatostatin receptors have been detected in the rat cerebellum during the first two postnatal weeks. Somatostatin binding sites are associated with a germinative matrix, the external granule cell layer, which generates the majority of the interneurons of the cerebellum. By using immature granule cells in primary culture, we could demonstrate that somatostatin binding sites are actually expressed by neuroblasts and correspond to authentic receptors negatively coupled to adenylate cyclase. Concurrently, studies on the distribution of PACAP receptors in the immature rat cerebellum showed the presence of a high concentration of binding sites in the external granule cell layer during the first two postnatal weeks. Pharmacological characterization of these binding sites showed that they correspond to type I PACAP receptors positively coupled to adenylate cyclase. The concomitant and transient expression of somatostatin and PACAP receptors by cerebellar neuroblasts in the external granule cell layer suggests that the two neuropeptides may be involved in the regulation of multiplication, migration and/or differentiation of neuroblasts. This hypothesis is also supported by the actions of somatostatin and PACAP on various transduction systems. In particular, the opposite effects of the two neuropeptides on adenylate cyclase activity suggest that somatostatin and PACAP may exert antagonistic actions.
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PMID:Somatostatin and pituitary adenylate cyclase-activating polypeptide (PACAP): two neuropeptides potentially involved in the development of the rat cerebellum. 786 80

Rat pancreas perfusion was performed to study the effects of pituitary adenylate cyclase activating polypeptide (PACAP) on pancreatic hormone release. Under the perfusate glucose concentration of 5.5 mmol/l, 0.1 nmol/l PACAP27 significantly stimulated both insulin and glucagon release. The degree of stimulation was in a dose dependent manner. The stimulation of insulin release was clearly dependent on the perfusate glucose concentration, when compared with 2.8, 5.5 and 8.3 mmol/l. The potency of PACAP38 on the stimulation of insulin release was greater than that of PACAP27 at 5.5 mmol/l of perfusate glucose concentration, but not at 8.3 mmol/l. No differences for glucagon and cAMP release were found between the two peptides. PACAP's stimulatory effects on insulin and glucagon release were completely abolished by an equimolar and ten times lower concentration of somatostatin, respectively. The physiologic significance of these potent effects of PACAP's islet hormones release must be clarified by further studies.
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PMID:Stimulatory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on insulin and glucagon release from the isolated perfused rat pancreas. 790 13

Pituitary adenylate cyclase activating polypeptide (PACAP38) stimulated growth hormone release as well as cAMP accumulation in a static rat primary pituitary cell culture in a dose-dependent manner with EC50 values of 1.9 +/- 0.4 nM (n = 13) and 0.9 +/- 0.3 nM (n = 5), respectively. The maximal GH response was observed between 5 to 15 min. Prolonged incubation (3 to 4 hrs) markedly reduced the stimulatory effect of PACAP38. The effect of PACAP38 on GH release was desensitized by pretreatment of the cells with PACAP38 or GRF, but not with PMA. The PACAP38-induced desensitization appeared to be time- and dose-dependent. Somatostatin (20 nM) inhibited PACAP-stimulated GH release through a cAMP-independent pathway.
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PMID:Pituitary adenylate cyclase activating polypeptide-induced desensitization on growth hormone release from rat primary pituitary cells. 790 58

Because of the enormous growth over the last three decades of research on the role of peptides in the brain, the need became apparent to determine the status of these compounds in terms of their current research interest. Since 1965, over a quarter of a million research papers have been published on peptides that have since been classified as neuroactive. The present study was undertaken to analyze systematically the yearly trends of research emphasis in neuroactive peptides as reflected by their individual frequency of publication by year, beginning in 1966. A computer analysis of the publication characteristics was carried out using the Medline data base in which the citation search was limited to the topic brain crossed with the topic mammal. One criterion for the inclusion of a given peptide in the analysis was a frequency of 25 or more citations following its discovery, as related to the mammalian brain. The 42 peptides that met this criterion were: adrenocorticotropic hormone, angiotensin II, atrial natriuretic factor, bombesin, bradykinin, calcitonin, calcitonin gene-related peptide, carnosine, beta-casomorphin, cholecystokinin, corticotropin-releasing factor, delta sleep-inducing peptide, dynorphin, beta-endorphin, Leu-enkephalin, Met-enkephalin, galanin, gastrin, glucagon, growth hormone, growth hormone-releasing factor, insulin, kyotorphin, beta-lipotropin, luteinizing hormone-releasing factor, melanocyte-stimulating hormone release inhibitory factor-1, alpha-melanocyte-stimulating hormone, motilin, neurokinin A, neurokinin B, neuropeptide Y, neurotensin, oxytocin, pituitary adenylate cyclase activating polypeptide, peptide HI, prolactin, secretin, somatostatin, substance P, thyroid-releasing hormone, vasopressin, and vasoactive intestinal peptide. An overall analysis of the 298,105 papers published on these 42 peptides since 1965 revealed that the research activity of 24,742, or 8.30%, of the studies, focused on their neuroactive properties. Taken as a whole, the research on neuroactive peptides reached a peak in 1986, as reflected by the total of 1793 papers published during that year. Although the level of publication has fluctuated between 1548 and 1774 research papers over the last 6 years, it is now clear that the trend in research on neuroactive peptides has reached an asymptote today that shows no sign of deviation. A temporal analysis year by year of individual publication profiles revealed three distinct trends: 1) peptides showed a slow development in research interest and did not exceed more than 15-30 publications per year; 2) peptides exhibited a steady increase in research activity over the years that continues today; and 3) peptides displayed an initial, often intense, research emphasis that inexplicably declined, in some cases precipitously, in the mid 1980s.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuroactive peptides: unique phases in research on mammalian brain over three decades. 800 41

The myotropic effect of pituitary adenylate cyclase-activating polypeptide (PACAP), a novel brain-gut peptide with high sequence homology to vasoactive intestinal polypeptide (VIP), was studied in the isolated guinea pig ileum in vitro. PACAP contracts the guinea pig ileum significantly more potently and efficiently compared with VIP. PACAP-induced contraction was abolished by tetrodotoxin, dynorphin, and somatostatin, partially reduced by atropine, and not affected by ganglionic and adrenergic blockade. The atropine-resistant component was sensitive to spantide, to the induction of tachyphylaxis with substance P, and to omega-conotoxin. Ileal strips desensitized to PACAP did not respond to VIP, although they maintained their sensitivity to PACAP after desensitization to VIP. COOH-terminal-truncated derivatives of PACAP exhibited full biological activity, although some of them showed substantially reduced potency. Deletion of NH2-terminal amino acids abolished biological activity. PACAP produced a concentration-dependent increase in the release of [3H]acetylcholine from longitudinal muscle-myenteric plexus preparations preloaded with [3H]choline. This effect was Ca2+ dependent, tetrodotoxin sensitive, and resistant to hexamethonium and scopolamine. In contrast, PACAP inhibited release of acetylcholine evoked by field stimulation. In summary, PACAP-induced contraction of the guinea pig ileum is mediated via release of acetylcholine and substance P through interaction with PACAP-1 and VIP/PACAP-2 receptors. PACAP has to be added to the list of myotropic neuropeptides of the gastrointestinal tract.
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PMID:PACAP is a stimulator of neurogenic contraction in guinea pig ileum. 836 12

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a new VIP-like brain-gut peptide. Its effects on the motility and secretory functions of the gastrointestinal system have been shown in previous studies. In this study we investigated the effect of intravenous PACAP on gastric acid secretion in conscious pylorus-ligated rats and in gastric fistula rats. PACAP showed significant inhibitory effects on pentagastrin- and histamine-stimulated gastric acid secretion, but no effect on basal or carbachol-stimulated secretion in pylorus-ligated rats. It did show dose-related inhibitory effects both on basal gastric acid secretion and on secretion stimulated by pentagastrin, histamine, or carbachol in gastric fistula rats. PACAP did not alter serum gastrin levels. Inhibition of prostaglandin synthesis with indomethacin and immunoneutralization of somatostatin with anti-somatostatin serum did not prevent the inhibitory effect of PACAP on gastric acid secretion in pylorus-ligated rats. We conclude that PACAP most likely has a direct effect on parietal cells and that this effect may be mediated, at least partially, by inhibition of the action of histamine on parietal cells.
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PMID:Effect of PACAP on gastric acid secretion in rats. 853 87

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) stimulated GH secretion in superfused rat anterior pituitary cell in vitro and in conscious male rats in vivo. PACAP-38-induced GH secretion was inhibited by PACAP-(6-38), an N-terminal-deleted analog, at 100-fold concentrations of PACAP-38 both in vitro and in vivo. In contrast, a GH-releasing hormone antagonist did not affect the action of PACAP-38 to stimulate GH release in vitro. Plasma GH increase induced by i.v. injection of 5-hydroxy-L-tryptophan (1 mg/100 g BW), a precursor of serotonin, was blunted by PACAP-(6-38) (1 nmol/100 g BW, i.v.), whereas spontaneous pulsatile GH secretion in conscious male rats, which is governed by hypothalamic GH-releasing hormone and somatostatin, was not affected by repeated i.v. injection of PACAP-(6-36). These findings suggest that PACAP-(6-38) is a potent antagonist of PACAP-38 to stimulate GH secretion both in vivo and in vitro. Taken together with the facts that PACAP-38 is highly concentrated in the hypothalamus and that is released into the hypophysial portal blood, our present findings suggest that PACAP-38 might play a stimulatory role on GH secretion induced by serotoninergic mechanisms in the rat.
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PMID:Involvement of pituitary adenylate cyclase-activating polypeptide in growth hormone secretion induced by serotoninergic mechanisms in the rat. 861 3

The colon cancer cell line HT29 is a useful model to study intestinal chloride secretion. These cells have both cAMP-activated and calcium-activated chloride channels. Changes in elemental content of the cells after stimulation with agonists were determined by X-ray microanalysis in the scanning or scanning transmission electron microscope. Exposure of HT29 cells to pituitary adenylate cyclase activating polypeptide-27 (PACAP) caused a transient decrease in the cellular Cl and K concentrations, indicating (net) efflux of chloride. The effect of PACAP is inhibited by somatostatin, which is known to inhibit cAMP-activated as well as calcium-activated chloride secretion and by U-73122, an inhibitor of phospholipase C. Alloxan, an inhibitor of adenylate cyclase, did not significantly affect the PACAP-induced loss of chloride. The calcium-chelating agent EGTA inhibited the PACAP-induced loss of chloride, indicating the need for extracellular calcium ions. Also vasointestinal polypeptide (VIP) caused a decrease of the cellular chloride concentration in HT29 cells. VIP-induced loss of chloride could be inhibited by pre-treating the cells with somatostatin or UK14,304, an alpha-2 adrenergic agonist that has been shown previously to inhibit purinergically activated chloride efflux. Our results indicate that there is cross-talk between the cAMP- and the calcium-activated pathways for chloride secretion in HT29 cells.
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PMID:Effects of pituitary adenylate cyclase activating polypeptide-27 (PACAP) and vasoactive intestinal polypeptide (VIP) on chloride in HT29 cells studied by X-ray microanalysis. 1007 2

Pituitary adenylate cyclase activating polypeptide (PACAP) is present in gastric nerves, and PACAP receptors (PAC1) are found on gastric enterochromaffin-like (ECL) cells. Expression of PAC1 splice variants in purified ECL cells was determined by RT-PCR. PACAP effects on ECL cells were analyzed by video imaging of [Ca(2+)](i) and histamine release; its effects on gastric glands were examined by confocal microscopy of [Ca(2+)](i) in ECL and parietal cells. PACAP action on D cells was measured by [Ca(2+)](i) and radioimmunoassay. PACAP effects on acid secretion were determined in fistula rats with or without neutralizing anti-somatostatin antibodies. All splice variants of PAC1 were found, but vasoactive intestinal polypeptide (VIP) receptor (VPAC) products were absent. PACAP-27 and -38 dose-dependently raise [Ca(2+)](i) in ECL cells, and stimulated histamine release. VIP had a much lower affinity, which demonstrates the presence of PAC1 but not VPAC. PACAP elevated [Ca(2+)](i) in ECL and parietal cells of superfused gastric glands, but only the parietal cell signal was inhibited by ranitidine, showing the absence of PAC1 on parietal cells, and demonstrating functional coupling between the cell types. PACAP and VIP stimulated calcium signaling and somatostatin release from D cells with almost equal efficacy. Acid secretion was stimulated after intravenous injection of PACAP into rats treated with somatostatin antibody. PACAP is a candidate as a mediator of neural regulation of acid secretion.
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PMID:PACAP type I receptor activation regulates ECL cells and gastric acid secretion. 1056 95


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