Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of gastrin and somatostatin secretion by intramural neurons was examined in the isolated vascularly perfused rat stomach. The optimal modalities of transmural electrical stimulation of the antrum were established to be 40 V and 10 Hz. Stimulation at increasing cycle durations (0.1-4 ms) caused increasing gastrin secretion that was progressively more resistant to atropine. The maximal gastrin response to 4-ms cycles was equal to the maximal response to methacholine. However, the response to methacholine was inhibited 70-90% by atropine, whereas the response to 4-ms cycles was inhibited by 15% only. Stimulation at all cycle durations caused a decrease in somatostatin secretion. Atropine converted the decrease to an increase, from which it was concluded that before atropine somatostatin secretion was the net result of cholinergic inhibition and noncholinergic stimulation of somatostatin. The results indicate that cholinergic and noncholinergic intramural neurons are predominantly but not exclusively activated by 0.1- and 4-ms cycles, respectively. The existence of distinct neurons was supported by results of stimulation of preganglionic vagal fibers with 0.2- and 4-ms cycles. The findings are consistent with a model according to which gastrin secretion is regulated by two interdependent intramural neurons: a cholinergic neuron that stimulates gastrin secretion indirectly by inhibition of somatostatin secretion and a noncholinergic neuron that stimulates gastrin secretion directly by release of a peptide stimulant, probably bombesin.
 ...
PMID:Regulation of gastrin and somatostatin secretion by cholinergic and noncholinergic intramural neurons. 612 24

Bombesin, acetylcholine, prostaglandins and somatostatin are all thought to be involved in the regulation of gastrin release and gastric secretion. We have studied the effects of low doses of atropine, 16-16(Me)2-prostaglandin E2 (PGE2) and somatostatin-14 on bombesin-stimulated gastrin release and gastric acid and pepsin secretion in conscious fistula dogs. For reference, synthetic gastrin G-17 was studied with and without somatostatin. Bombesin, in a dose-related manner, increased serum gastrin, which in turn stimulated gastric acid and pepsin secretion in a serum gastrin, concentration-dependent manner. Somatostatin inhibited gastrin release by bombesin as well as the secretory stimulation by G-17; the combination of sequential effects resulted in a marked inhibition of bombesin-stimulated gastric acid and pepsin secretion. PGE2 also strongly inhibited gastrin release and acid and pepsin secretion. Atropine had no significant effect on gastrin release, but greatly inhibited gastric secretion. Thus somatostatin and PGE2 inhibited at two sites, gastrin release and gastrin effects, while atropine affected only the latter.
 ...
PMID:Somatostatin, prostaglandin E2 and atropine inhibition of the gastric actions of bombesin in the dog. 614 3

Postvagotomy hypergastrinemia persists in the isolated perfused rat stomach, but its cause is unknown. The possible role of cholinergic nervous pathways was investigated in the isolated vascularly perfused rat stomach after vagotomy. Atropine and hexamethonium, but not propranolol, inhibited postvagotomy hypergastrinemia. A nervous mechanism involving acetylcholine was further suggested by the inhibitory action of methionine-enkephalin on gastrin release after vagal section. Methacholine, a muscarinic receptor agonist, only weakly stimulated gastrin release from vagotomized stomachs when compared with shamoperated controls, indicating that a cholinergic drive was already in place. Immunocytochemical studies of antral tissue following vagotomy indicated that numbers of gastrin-containing cells (G-cells) were not increased after vagotomy but exhibited reduced intensity of gastrin staining when compared with control stomachs. It was concluded that basal hypergastrinemia may result from increased stimulation of a normal G-cell population by a cholinergic mechanism at the ganglionic level.
 ...
PMID:Gastrin release from isolated perfused rat stomach after vagotomy. 614 16

Using a newly developed system for culturing canine fundic mucosal cells, we examined regulation of the secretion of somatostatinlike immunoreactivity (SLI) by cholinergic and adrenergic transmitters. Enzyme-dispersed canine fundic mucosa cells were enriched in SLI content by counterflow elutriation and cultured on collagen for 42 h. Epinephrine alone, and in combination with gastrin, stimulated SLI secretion in a dose-dependent fashion. Propranolol did not alter the response to dibutyryl cAMP or gastrin but produced a parallel, rightward shift of the epinephrine dose-response curve with the dissociation constant (Ki) determined to be 14 nM by nonlinear curve fitting. Phentolamine, an alpha-adrenergic antagonist, enhanced SLI secretion in response to epinephrine, an effect reversed by the alpha 1-agonist methoxamine but not by the alpha 2-agonist clonidine. However, neither methoxamine nor clonidine alone inhibited the response to the beta-selective adrenergic agonist isoproterenol; thus, the existence of an adrenergic alpha 1-inhibitory receptor remained uncertain. Carbachol noncompetitively inhibited SLI secretion stimulated by gastrin, epinephrine, and dibutyryl cAMP. Atropine produced a parallel rightward shift of the carbachol dose-response curve (Ki = 0.4 nM). Pirenzepine also inhibited the effects of carbachol (Ki = 35 nM). Our studies suggest that SLI-containing cells in the canine fundic mucosa possess stimulatory beta-adrenergic receptors and inhibitory muscarinic receptors.
 ...
PMID:Autonomic regulation of somatostatin release: studies with primary cultures of canine fundic mucosal cells. 614 98

We used membrane preparations of rat oxyntic gland mucosa to test the binding of various gastrin analogues to the gastrin receptor. Using [125I]15-Leu G-17 as a marker, a concentration of 4 X 10(-9) M unlabeled G-17 inhibited binding 50%. The tetra-, penta-, and hexapeptides of gastrin caused similar 50% inhibitions of binding at concentrations of 1 X 10(-7) M, 3 X 10(-8) M, and 7 X 10(-9) M, respectively. The heptapeptide caused only slightly less inhibition than G-17, whereas the decapeptide was equivalent in potency. Neither the G-17 nor G-34 that had the active tetrapeptide removed caused 50% inhibition of binding. When compared to G-17, these analogues produced only a 25% inhibition of binding at concentrations of 10(-8) M. We also failed to inhibit binding more than 25% when we used an analogue that had the amide removed from the C-terminal phenylalanine. Atropine, metiamide, and mepyramine did not alter the binding of gastrin to receptor. The results of binding specificity approximate the changes in biological potency associated with these compounds. This study adds further support that the gastrin receptor in question is responsible for the physiological effects of the hormone.
 ...
PMID:Mucosal gastrin receptor. IV. Binding specificity. 625 80

During modified sham feeding (MSF) the role of endogenous gastric acid secretion and the influences of the autonomic nervous system on the release of pancreatic polypeptide (PP) and gastrin have been studied in 12 healthy subjects (aged 24-38 years). Sham feeding was performed without pretreatment (control) and after pretreatment with 400 mg cimetidine, 80 mg propranolol (both given orally) or 1 mg atropine administered subcutaneously 60 min prior to sham feeding. MSF induced a significant increase (about 100%) in PP release. Its early peak was reduced by pretreatment with propranolol whereas cimetidine had no effect. Atropine completely abolished the PP response. Gastrin release was stimulated by MSF only after prior administration of cimetidine and, to a lesser extent, after atropine pretreatment. It is concluded that: (1) the PP release after stimulation is under strong cholinergic control but is also mediated--particularly in the early phase--by adrenergic mechanisms; (2) endogenously released acid during vagal stimulation plays a minor role in the modulation of PP secretion, but (3) masks gastrin response to MSF.
 ...
PMID:Pancreatic polypeptide and gastrin release during sham feeding in man. 648 44

The effects of 1-h infusions of bombesin and gastrin releasing peptide (GRP) at 50 pmol/kg per h and neurotensin at 100 pmol/kg per h on gastrin, pancreatic polypeptide (PP) and neurotensin release in man were determined following either saline or atropine infusion (20 micrograms/kg). Bombesin produced a rise in plasma neurotensin from 32 +/- 6 to 61 +/- 19 pmol/l and of PP from 26 +/- 8 to 36 +/- 7 pmol/l. There was a further rise of plasma PP to 50 +/- 13 pmol/l after cessation of the infusion. GRP had no significant effect on plasma neurotensin, but compared to bombesin, produced a significantly greater rise in plasma PP from 34 +/- 6 to 66 +/- 19 pmol/l during infusion. There was no post-infusional increase. At this dose, GRP was as effective as bombesin in releasing gastrin, although unlike bombesin its effect was enhanced by atropine. Neurotensin produced a rise in plasma PP from 17 +/- 4 to 38 +/- 8 pmol/l. Atropine blocked the release of PP during GRP and neurotensin infusion. Atropine had no effect on neurotensin or PP release during bombesin infusion, but did block the rise in plasma PP following bombesin infusion. We conclude that, in contrast to meal-stimulated neurotensin release, bombesin-stimulated neurotensin release is cholinergic independent. Despite structural homology, bombesin and GRP at the dose used are dissimilar in man in their actions and sensitivity to cholinergic blockade.
 ...
PMID:The effect of atropine on bombesin and gastrin releasing peptide stimulated gastrin, pancreatic polypeptide and neurotensin release in man. 664 89

We studied the effects of atropine, both in the basal state and after stimulation by modified sham feeding (MSF), and the effect of MSF alone, on the plasma gastrin and pancreatic polypeptide (PP) responses in 8 healthy human subjects. Atropine 1 mg in the basal state had no effect on the plasma gastrin concentrations but led to significant decrease in plasma PP concentrations. Plasma gastrin response to MSF was negligible but increased by atropine. The plasma PP level was markedly increased by MSF, and was antagonized by atropine. This study shows that the release of plasma PP during basal state and after MSF is under the control of the vagal-cholinergic mechanism, but plasma gastrin is controlled by a different mechanism.
 ...
PMID:Plasma gastrin and pancreatic polypeptide response to atropine and sham feeding in man. 671 46

The cephalic phase of pancreatic secretion in humans was investigated using modified sham feeding and a duodenal perfusion system. Studies performed in 5 normal volunteers were designed so that trypsin and bicarbonate outputs during sham feeding, with or without pretreatment with atropine, were compared to "maximal" pancreatic secretory response to exogenous stimulation with caerulein and secretin. The role of gastric acid entry to the duodenum in mediating cephalic responses was assessed by a comparison between outputs observed when gastric aspiration (congruent to 80% efficient) was used alone and when acid entry was completely abolished by combining gastric aspiration with cimetidine pretreatment. To evaluate the role, if any, of gut hormone release in the pancreatic secretory response to sham feeding, plasma gastrin and cholecystokinin concentrations were monitored throughout. Trypsin outputs during sham feeding were 31.9 +/- 10.45 kallikrein inactivator units per 30 min, equivalent to four times basal output and 92% of maximal, but were only 54% maximal in subjects pretreated with cimetidine. Atropine suppressed basal trypsin output and abolished the response to sham feeding (4.98 +/- 3.89 kallikrein inactivator units per 30 min). A modest increase in bicarbonate secretion during sham feeding (3.30 +/- 1.97 mmol/30 min versus basal of 0.68 +/- 0.74 mmol/30 min, p = 0.5) was not influenced by atropine but was abolished by cimetidine pretreatment. No significant changes in plasma gastrins were observed in these studies and plasma cholecystokinins remained undetectable throughout. We conclude that there is tonic vagal stimulation of trypsin secretion, and that sham feeding markedly increases trypsin output, which is augmented further by acid entry into the duodenum. There is no direct effect of cephalic stimulation on bicarbonate secretion or on gastrin or cholecystokinin release.
 ...
PMID:Sham feeding and pancreatic secretion. Evidence for direct vagal stimulation of enzyme output. 672 52

We used acute anesthetized dogs to investigate the role of cholinergic receptors in the relationship between antral immunoreactive (I) gastrin release and antral motility. Electrical stimulation of extrinsic nerves via the cervical vagus or the nerve of Latarjet appeared to increase I gastrin release and antral motility by separate pathways as blockade of muscarinic receptors, i.e., atropinization inhibited motility but did not alter I gastrin release. On the other hand, blockade of nicotinic receptors by hexamethonium treatment obliterated I gastrin release induced by stimulation of the extrinsic nerves but only reduced motility. Field stimulation of intrinsic nerves via serosal electrodes also increased both I gastrin release and local motility. Since hexamethonium treatment only slightly reduced both I gastrin release and motility and atropinization eliminated both during field stimulation, the presence of a muscarinic receptor in the final pathway for each is proposed. Atropine eliminated carbachol-induced I gastrin release and motility increases, even in the presence of nerve blockade by tetrodotoxin. This suggests that this muscarinic receptor is on the smooth muscle cell itself and possibly on the gastrin cell. However a proposed role of the somatostatin cell in controlling gastrin release is also consistent with these data. Thus, both an intrinsic cholinergic and a separate extrinsic noncholinergic pathway are involved in antral release of I gastrin but initiation of motility appears to involve a final common pathway terminating in a muscarinic receptor on the smooth muscle cell.
 ...
PMID:Cholinergic control of canine antral immunoreactive gastrin release and motility. 712 12


<< Previous 1 2 3 4 5 6 7 8 9 Next >>