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M L Schubert

Publications and source records attributed to M L Schubert.

63 records · Page 4Linked to original sources
PubMed1988

Identical patterns of somatostatin secretion from isolated antrum and fundus of rat stomach.

The patterns of somatostatin secretion from the fundus, the main source of somatostatin, and the antrum, the site of paracrine regulation of gastrin secretion, were examined using perifused antral and fundic segments from rat stomach. Gastrin secretion fundic segments from rat stomach. Gastrin secretion could be obtained from antral segments only. Somatostatin secretion was obtained from both antral and fundic segments. 1,1-Dimethyl-4-phenylpiperazinium (DMPP) (10(-5) and 10(-4) M) and bombesin-14 (10(-8) and 10(-6) M) caused concentration-dependent increases in somatostatin secretion that were of the same magnitude in antral and fundic segments. These increases were also of the same magnitude as those obtained in the vascularly perfused whole stomach. Atropine (3 X 10(-7) M) inhibited the somatostatin response to DMPP (10(-4) M) to the same extent in antral (50 +/- 12% inhibition) and fundic (55 +/- 12% inhibition) segments. Hexamethonium (10(-5) M) also inhibited the response to DMPP to the same extent in antral (80 +/- 9%) and fundic (78 +/- 19%) segments. Methacholine caused a typically muscarinic decrease in somatostatin secretion that was of the same magnitude in antral (27 +/- 6%) and fundic (25 +/- 6%) segments. The identical patterns of somatostatin secretion from the two regions of the stomach imply that somatostatin secretion measured in the vascularly perfused whole stomach is a valid reflection of somatostatin secretion by the antrum.

Animals↗
PubMed1987

Paracrine regulation of gastric acid secretion by fundic somatostatin.

The isolated, luminally perfused mouse stomach was used to determine whether somatostatin cells located in proximity to parietal cells exert a paracrine influence on acid secretion. Acid secretion in response to histamine and pentagastrin was accompanied by a dose-dependent increase in somatostatin secretion. Incubation of the stomach with somatostatin antiserum (final dilution 1:100), but not with normal serum, augmented significantly basal and secretagogue-stimulated acid secretion. The augmentation was most evident with submaximal stimuli (92 +/- 18%, P less than 0.01, with 15 microM pentagastrin and 160 +/- 6%, P less than 0.001, with 5 microM histamine) and least evident with maximal stimuli (30 +/- 12%, P less than 0.05, with 200 microM histamine). The acid response to submaximal field stimulation (10 V, 20 Hz, 0.5 ms), which was accompanied by an increase in somatostatin secretion, was also augmented by somatostatin antiserum (115 +/- 12%, P less than 0.01), whereas the response to maximal field stimulation (20 V, 20 Hz, 0.5 ms), which was accompanied by a decrease in somatostatin secretion, a typically cholinergic effect, was not augmented further. It is concluded that fundic somatostatin modulates the acid secretory response to paracrine (histamine), hormonal (gastrin), and neural (acetylcholine) stimuli and that cholinergic stimulation of acid secretion reflects both the direct effect of acetylcholine on the parietal cell and its ability to eliminate the paracrine restraint exerted by somatostatin.

Animals↗
PubMed1987

Neural regulation of gastrin and somatostatin secretion in rat gastric antral mucosa.

A muscle-stripped mucosal sheet obtained from rat antrum was mounted in an Ussing chamber and used to examine the regulation of gastrin and somatostatin secretion by antral neurons. The neurons were activated pharmacologically with 1,1-dimethyl-4-phenylpiperazinium (DMPP) or electrically by field stimulation using aluminum foil electrodes layered over the edge of the mucosal sheet. Field stimulation caused an increase in gastrin and somatostatin secretion that was dependent on the strength of the stimulus (10-30 V). Field stimulation at 30 V, 10 Hz, 4 ms caused a sixfold increase in gastrin and a twofold increase in somatostatin secretion that were nearly abolished by tetrodotoxin (85-89% inhibition). Atropine partially inhibited the gastrin response (34 +/- 6%) but had no effect on the somatostatin response. DMPP caused lesser, though significant, increases in gastrin (166%) and somatostatin (83%) secretion that were nearly abolished by hexamethonium (84-91%) but were not significantly affected by atropine. The increase in somatostatin secretion caused by DMPP and field stimulation, as well as the resistance of gastrin and somatostatin secretion to atropine, was consistent with preferential activation of noncholinergic neurons at the stimulatory modalities used. The pattern and magnitude of gastrin and somatostatin response to pharmacological and electrical stimulation of antral neurons were similar to those previously observed in the vascularly perfused whole rat stomach.

Animals↗
PubMed1985

Inhibition of neurally mediated gastrin secretion by bombesin antiserum.

In vitro studies on the vascularly perfused rat stomach have shown that gastrin secretion is regulated by intramural cholinergic and noncholinergic neurons. We have postulated that bombesin (gastrin-releasing peptide), a known gastrin stimulant present in antral mucosal nerve fibers, is the most likely candidate for noncholinergic transmitter. Bombesin antiserum (final dilution, 1:150) but not control serum added to the vascular perfusate inhibited the gastrin response to 1,1-dimethyl-4-phenylpiperazinium by 59 +/- 17% (P less than 0.01) and to electrical field stimulation by 60 +/- 16% (P less than 0.01), and its effect was additive to that of 10(-7) M atropine (75-94%), thus accounting for the greater part of neurally induced gastrin secretion. The effects of atropine and bombesin antiserum on somatostatin secretion were consistent also with blockade of cholinergic and noncholinergic neurons, respectively. The results indicate that bombesin and acetylcholine are the main intramural neural regulators of gastrin and somatostatin secretion. Acetylcholine acts predominantly to decrease the paracrine secretion of somatostatin, thereby eliminating the continuous restraint of somatostatin on gastrin secretion and enabling bombesin to exert its potent stimulatory effect on gastrin secretion.

Acetylcholine↗
PubMed1982

Regulation of gastrin and somatostatin secretion by cholinergic and noncholinergic intramural neurons.

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.

Animals↗
PubMed1982

Regulation of gastrin and somatostatin secretion by intramural neurons: effect of nicotinic receptor stimulation with dimethyl-phenylpiperazinium.

The nicotinic receptor agonist, 1,1-dimethyl-4-phenylpiperazinium was used to examine the intramural neural regulation and the functional linkage of gastrin and somatostatin the isolated vascularly perfused rat stomach. 1,1-Dimethyl-4-phenylpiperazinium (10(-5) to 10(-4) M) caused a biphasic dose-dependent increase in gastrin secretion. The gastrin response was abolished by hexamethonium but only partly inhibited (35% at the higher dose of 1,1-dimethyl-4-phenylpiperazinium) by atropine. The same dose of atropine inhibited the maximal gastrin response to the muscarinic agonist, methacholine, by 80%. From this it was concluded that 1,1-dimethyl-4-phenylpiperazinium activates intramural cholinergic and noncholinergic neurons to cause gastrin secretion, 1,1-dimethyl-4-phenylpiperazinium also caused a biphasic, dose-dependent increase in somatostatin secretion. The somatostatin response was completely inhibited by atropine and hexamethonium. Since muscarinic cholinergic agonists cause inhibition of somatostatin secretion, the observed net increase in somatostatin suggests that 1,1 dimethyl-4-phenylpiperazinium activated predominantly a noncholinergic stimulatory neuron. It is hypothesized that this neuron is identical to the gastrin-stimulating noncholinergic neurons and that it releases bombesin, a stimulant of gastrin and somatostatin secretion known to be present in gastric mucosal nerve terminals. The results of this study are consistent with a previously proposed model according to which gastrin secretion is regulated by the activity of two interdependent intramural neurons: a cholinergic neuron that causes gastrin secretion via inhibition of somatostatin and a noncholinergic neuron that releases a synergistic, direct stimulant of gastrin secretion, most likely bombesin.

Animals↗
PubMedDate not supplied

Neural, hormonal, and paracrine regulation of gastrin and acid secretion.

Physiological stimuli from inside and outside the stomach coverage on gastric effector neurons that are the primary regulators of acid secretion. The effector neurons comprise cholinergic neurons and two types of non-cholinergic neurons: bombesin/GRP and VIP neurons. The neurons act directly on target cells or indirectly by regulating release of the hormone, gastrin, the stimulatory paracrine amine, histamine, and the inhibitory paracrine peptide, somatostatin. In the antrum, cholinergic and bombesin/GRP neurons activated by intraluminal proteins stimulate gastrin secretion directly and, in the case of cholinergic neurons, indirectly by eliminating the inhibitory influence of somatostatin (disinhibition). In turn, gastrin acts on adjacent somatostatin cells to restore the secretion of somatostatin. The dual paracrine circuit activated by antral neurons determines the magnitude of gastrin secretion. Low-level distention of the antrum activates, preferentially, VIP neurons that stimulate somatostatin secretion and thus inhibit gastrin secretion. Higher levels of distention activate predominantly cholinergic neurons that suppress antral somatostatin secretion and thus stimulate gastrin secretion. In the fundus, cholinergic neurons activated by distention or proteins stimulate acid secretion directly and indirectly by eliminating the inhibitory influence of somatostatin. The same stimuli activate bombesin/GRP and VIP neurons that stimulate somatostatin secretion and thus attenuate acid secretion. In addition, gastrin and fundic somatostatin influence acid secretion directly and indirectly by regulating histamine release. Acid in the lumen stimulates somatostatin secretion, which attenuates acid secretion in the fundus and gastrin secretion in the antrum.

Animals↗
PubMedDate not supplied

Pharmacotherapy for acid/peptic disorders.

In the 1970s, the identification of the histamine H2-receptor by Black and the subsequent development of histamine H2-receptor antagonists revolutionized our understanding and treatment of acid/peptic disorders. More recently, the identification of hydrogen-potassium-stimulated adenosine triphosphatase (H+/K(+)-ATPase) as the proton pump of the parietal cell and the recognition of the prominent role of Helicobacter pylori in the pathogenesis of duodenal and gastric ulceration have heralded a new revolution in our understanding and treatment of these disorders. Substituted benzimidazole compounds (omeprazole, lansoprazole and pantoprazole) that covalently bind to and inactivate the proton pump allow complete and prolonged inhibition of acid secretion. Not only can peptic ulcers now be healed more rapidly with proton pump inhibitors, but refractory ulcers have all but disappeared. Eradication of H. pylori with antibiotics offers, for the first time, a permanent cure for most duodenal and many gastric ulcers.

Anti-Ulcer Agents↗