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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nerve terminals in pancreatic islets and ganglia containing cholecystokinin (CCK)/gastrin-like peptides are particularly abundant in the cat. In order to elucidate the possible origin and molecular nature of the peptides in these nerves, extracts of the feline pancreas, vagus, sympathetic trunk, and celiac-superior mesenteric ganglion were examined by gel chromatography monitored by sequence-specific radioimmunoassays. Small amounts of CCK-33 and CCK-8 were present in the pancreatic terminals. In the vagus and the sympathetic trunk, CCK, mainly as CCK-8, occurred in concentrations of 3.5 and 3.7 pmol/g. The celiac-superior mesenteric ganglion contained 40 pmol CCK/g distributed in five forms, including a predominant CCK-8-like component and a component eluting like CCK-4. Gastrins were not detected in the nervous structures. The results suggest that the celiac-superior mesenteric ganglia, the vagal nerves and the sympathetic trunks all may contribute to the CCK nerve terminals in the feline pancreas.
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PMID:The molecular nature of cholecystokinin in the feline pancreas and related nervous structures. 646 84

The gastrointestinal peptide hormones, gastrin and cholecystokinin (CCK), display four molecular characteristics. 1) Homology. Sequences of the primary structures are identical. Because the identity comprises the active site, the homology is functionally important. The homology reflects evolution from a common ancestor. 2) Heterogeneity. Each hormone exists in different molecular forms in any single species. The heterogeneity comprises both variations in lengths of the polypeptide backbone, "macroheterogeneity," and derivatizations of single amino acid residues, "microheterogeneity." Both types of modification govern the biological potency. The heterogeneity reflects enzymatic modifications of the primary ribosomal translation product. 3) Ubiquity. Each hormone is synthetized in different cell types, which are localized in gastrointestinal as well as extra-gastrointestinal tissues. The cell type determines the route by which the active peptide(s) reaches its target, either via blood (endocrine secretion) or by local release (neurocrine and paracrine secretion). Inasmuch as all cells contain gastrin and CCK genes, the variable expression probably reflects differentiation in development of the posttranscriptional biosynthetic machinery. 4) Differential principality. In different tissues and cells, different molecular forms may predominate. Moreover, one form is more potent with respect to one effect (e.g., CCK-8 in relation to pancreatic exocrine secretion), whereas another form (CCK-4) is more potent with respect to another effect (pancreatic endocrine secretion). Together the differential principality and secretory routes (blood borne or local) ensure that gastrin and CCK peptides regulate their targets with optimal effect in spite of the heterogeneity and wide distribution, which otherwise might cause disturbing interactions and subsequent inefficacy. The key to a better understanding of the basis characteristics is knowledge about the evolution and expression of the structural gene(s) for gastrin and CCK. Acquisition of such knowledge will be of considerable value, since available evidence suggests that the gastrin-CCK system is a good model for general features of regulatory peptides.
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PMID:Four basic characteristics of the gastrin-cholecystokinin system. 701 99

Using sequence-specific radioimmunoassays, the quantities and molecular nature of cholecystokinin (CCK) have been determined in extracts of porcine duodenal mucosa and in the vascular perfusate from the isolated porcine duodenum. The basal concentration of CCK in the perfusate was 84 pM equiv. CCK-8 (mean; range: 32-173 pM, n = 5). After intraluminal stimulation with amino acids, acidified fat emulsions and hydrochloric acid, the concentrations increased 2--5-fold. Both in the basal and stimulated state the concentrations of the related hormone, gastrin, were below 5 pM equiv. gastrin-17. CCK in the perfusate was concentrated by affinity-chromatography using antibodies directed against the bioactive C-terminus. Subsequent gel chromatography revealed a form with a size like or slightly larger than the C-terminal dodecapeptide (CCK-12), a predominant form resembling the C-terminal octapeptide (CCK-8), and a form resembling the C terminal tetrapeptide (CCK-4). The duodenal mucosa contained in addition CCK-33, -39 and CCK-peptides with further N-terminal extensions. The results suggest that small CCK peptides are the principal circulating forms, while CCK-33 and larger forms are biosynthetic precursors.
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PMID:The molecular nature of vascularly released cholecystokinin from the isolated perfused porcine duodenum. 705 60

1. The cardiovascular actions of cholecystokinin and related peptides were investigated in the pithed rat. The receptors and the mechanisms involved in these experiments were characterized. 2. Sulphated cholecystokinin octapeptide (sCCK-8, 0.1-100 nmol kg-1, i.v.) elicited a dose-dependent bradycardia and increase in mean arterial blood pressure. Neither gastrin-17 nor pentagastrin had any effect at concentrations up to 100 nmol kg-1. 3. Both the pressor response and bradycardia elicited by sCCK-8 were reduced by the selective CCKA receptor antagonists, devazepide (0.5-50 nmol kg-1) and lorglumide (1-7 mumol kg-1). The selective CCKB receptor antagonists, CI-988 (1 mumol kg-1) and L-365,260 (15 mumol kg-1) did not inhibit the effects of sCCK-8. 4. The pressor response induced with sCCK-8 was reduced by treatment with either phentolamine (3 mumol kg-1) or guanethidine (2 mumol kg-1) and was unaffected by treatment with propranolol, atropine or hexamethonium. The pressor response also persisted following bilateral adrenalectomy. 5. The bradycardia induced with sCCK-8 was unaffected by treatment with phentolamine, propranolol, guanethidine, atropine, hexamethonium or bilateral adrenalectomy. 6. The tetrapeptide of cholecystokinin (CCK-4) elicited a dose-dependent pressor response but did not induce bradycardia. The pressor response was unaffected by devazepide (50 nmol kg-1), L-365260 (15 mumol kg-1) or phentolamine (3 mumol kg-1). 7. In the pithed rat, sCCK-8 acted via CCKA receptors to increase arterial blood pressure indirectly, at least in part, through activation of alpha-adrenoceptors. The observed bradycardia was also mediated byCCKA receptors but possibly through a direct action on the heart.
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PMID:Characterization of the receptors and mechanisms involved in the cardiovascular actions of sCCK-8 in the pithed rat. 758 87

Cholecystokinin (CCK), a gastrin-like neuropeptide, exists in the central nervous system in several forms. The octapeptide (CCK-8) occurs in predominantly sulfated form (CCK-8S), and the tetrapeptide (CCK-4) occurs in smaller but significant quantities. This review highlights recent developments in preclinical and clinical research into the potential role for CCK in mediating anxiety states. Relevant animal and human studies of administration of CCK agonists are discussed, as well as recent data regarding the concentration of CCK-8S in cerebrospinal fluid from patients with panic disorder, bulimia nervosa, and obsessive compulsive disorder. Finally, the development of agents that specifically antagonize CCK receptors will be described, as will potential therapeutic uses for these new compounds.
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PMID:Neuropeptides and anxiety: focus on cholecystokinin. 831 13

We found that GH3 cells, a rat anterior pituitary tumor cell line, expressed a single class of high-affinity binding sites for radiolabeled cholecystokinin octapeptide (CCK-8) with a Kd of 48 pM. The binding sites had high affinity for CCK-8, CCK-4, gastrin I, and L-365,260 (CCK-B antagonist), and had low affinity for devazepide (CCK-A antagonist), indicating that the binding sites are CCK-B receptors. GTP and its stable analogues inhibited radiolabeled CCK-8 binding to GH3 cell membranes, suggesting a coupling of CCK-B receptors to a G-protein.
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PMID:GH3 cells, an anterior pituitary cell line, express CCK-B receptors. 833 61

Cholecystokinin (CCK) has not been isolated from chicken gut yet and there has been no study on the effects of chicken gastrin (CG), the only gastrin/CCK peptide isolated from avian gut, on gastrointestinal motility. The main objective was to study the effects of CCK and CG on gastroduodenal motility and coordination in chickens. Electrodes for electromyography were implanted in the stomach and proximal and distal duodenum of 4 wk old chickens. Sulphated CCK-octapeptide (CCK8) (10(-10) to 10(-8) moles/kg), CCK-tetrapeptide (CCK4) (2 x 10(-10) to 2 x 10(-8) moles/kg) and CG (3 x 10(-10) to 10(-8) moles/kg) were given in a 10 min i.v. infusion. All these peptides induced a dose-dependent inhibition of gastric motility. CCK8 induced a duodenal hyperactivity whereas CCK4 and CG induced a duodenal inhibition. Neither the CCK-A receptor antagonist L364,718 nor the CCK-B receptor antagonist L365,260 (10(-9)-10(-7) moles/kg) antagonized CCK8 actions. From these results we suggest that the receptors mediating CCK effects are different from those of mammals. The site of action for these peptides is the same in the stomach whereas in the duodenum there are two different ones, one mediating excitation and the other inhibition. These results suggest a physiological role for CCK regulating gastroduodenal motility in birds.
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PMID:Effects of cholecystokinin and gastrin on gastroduodenal motility and coordination in chickens. 835 59

1. The cholecystokinin receptors mediating motor responses in a novel smooth muscle preparation from the corpus region of the guinea-pig stomach have been characterized by use of five agonist peptides and the antagonists CI-988, L-365,260 and devazepide. 2. Mucosa-denuded strips of circular muscle were contracted in a concentration-dependent manner by the five cholecystokinin (CCK)-related peptides CCK-8S, pentagastrin, gastrin-I, CCK-8US and CCK-4. 3. CI-988 was a powerful antagonist of the response to pentagastrin with an affinity (pKB = 9.49) similar to that obtained in CCKB receptor binding assays. With CCK-8S as the agonist, CI-988 was approximately 1000 fold less powerful as an antagonist. 4. Devazepide powerfully blocked responses to CCK-8S with an affinity (pKB = 9.54) that was in agreement with reported functional data obtained in pancreatic amylase secretion studies, a system exhibiting CCKA receptor activity. Devazepide displayed lower affinity against pentagastrin than against CCK-8S. 5. CI-988 blocked responses to pentagastrin in an insurmountable manner in the presence of 3 nM devazepide; a concentration previously shown to block the CCKA receptor. The nature of the antagonism observed with L-365,260 was unaltered by the presence of devazepide. 6. The guinea-pig stomach corpus smooth muscle preparation contains both subtypes of CCK receptor and will be useful as a pharmacological tool for investigating the functional effects of novel CCK ligands.
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PMID:Characterization of CCK receptors in a novel smooth muscle preparation from the guinea-pig stomach by use of the selective antagonists CI-988, L-365,260 and devazepide. 840 44

The effect of cholecystokinin octapeptide (CCK-8) was examined in guinea-pig celiac ganglion (CG) neurons in primary culture using standard intracellular recording techniques. Sulfated CCK-8 (CCK-8S; 1 microM) evoked slow depolarizing responses in 94% of CG neurons tested. In contrast, membrane potential was not affected by nonsulfated CCK-8 (CCK-8NS; 1 microM), CCK tetrapeptide (CCK-4; 1 microM), or gastrin (1 microM). The selective CCKA receptor antagonist L 364,718 potently inhibited CCK-8S-induced slow depolarizations (IC50 2.9 pM). In contrast, the selective CCKB receptor antagonist L 365,260 was a weak inhibitor of CCK-8S-induced slow depolarizations (IC50 1.3 microM). The depolarizing responses to CCK-8S were associated with an average increase in cell input resistance of 61%. Single electrode voltage clamp experiments indicated that CCK-8S-induced depolarizations were associated with a slow inward shift in holding current. Thus, the present findings indicate that guinea-pig cultured CG neurons are endowed with excitatory CCKA receptors the activation of which elicits a decrease in membrane conductance, thereby resulting in slow depolarizations.
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PMID:CCKA receptors mediate slow depolarizations in cultured mammalian sympathetic neurons. 845 96

1. Virginiamycin, a macrolide reported to bind selectively to CCKB/gastrin receptors has been studied in a functional test, namely cholecystokinin-induced contraction of guinea-pig ileum myenteric plexus (LMMP). 2. Virginiamycin (1-10 microM) antagonized the selective CCKB agonist cholecystokinin tetrapeptide (CCK-4). The antagonism appeared not to be competitive as the highest concentration (10 microM) caused a reduction of its maximal effect. An apparent pA2 of 6.64 +/- 0.06 (s.e.) could be estimated if this depression was ignored. The selective CCKB antagonist, L-365,260 (0.01-0.3 microM) antagonized competitively the CCK-4 induced contraction and a pKB of 8.60 +/- 0.16 (s.e.) was estimated. 3. The combined dose-ratio analysis for virginiamycin, tested at 3 and 10 microM in association with 0.03 and 0.1 microM L-365,260, respectively, resulted in observed log dose-ratios of 1.39 and 1.53. That was consistent with both antagonists acting on the same receptor in LMMP. 4. These data, represent the first evidence of the antagonism of virginiamycin in a functional assay and they support the hypothesis of homogeneity between CCKB receptors in the CNS and in peripheral tissues.
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PMID:Analysis of the CCKB receptor antagonism of virginiamycin in guinea-pig ileum longitudinal myenteric plexus. 848 26


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