Modulatory glucose effect on bombesin-like immunoreactivity and gastrin secretion from isolated perfused 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.

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Peptone stimulates gastrin secretion from the stomach by activating bombesin/GRP and cholinergic neurons

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1992.262.4.g685 ◽

1992 ◽

Vol 262 (4) ◽

pp. G685-G689 ◽

Cited By ~ 11

Author(s):

M. L. Schubert ◽

D. H. Coy ◽

G. M. Makhlouf

Keyword(s):

Cholinergic Neurons ◽

Rat Stomach ◽

Gastrin Releasing Peptide ◽

Gastrin Secretion ◽

Somatostatin Secretion ◽

Luminal Perfusion

The mechanism by which partly digested protein (peptone) stimulates gastrin secretion was examined in isolated antral tissues with intact intramural innervation. In the isolated vascularly perfused rat stomach, luminal perfusion with 0.5% peptone increased gastrin (62 +/- 14 pg/min; P less than 0.01) and decreased somatostatin (74 +/- 19; P less than 0.01) secretion. The axonal blocker tetrodotoxin (TTX) abolished the gastrin and somatostatin responses indicating that the responses were neurally mediated. Atropine partly inhibited the gastrin response (50%) and converted the somatostatin response to an increase above basal level. The selective bombesin/gastrin-releasing peptide (GRP) antagonist [Leu13-psi(CH2NH)-Leu14]-bombesin partly inhibited the gastrin response (65%) and caused a further decrease in somatostatin secretion. A combination of atropine and the bombesin/GRP antagonist, like TTX, abolished the gastrin and somatostatin responses. The pattern of response to peptone in superfused antral segments was identical to that in the vascularly perfused stomach. In fundic segments that do not secrete gastrin, the somatostatin response to peptone alone and with various antagonists was identical to that in antral segments. The results indicate that peptone stimulates gastrin secretion by activating stimulatory cholinergic and bombesin/GRP neurons. Cholinergic neurons stimulate gastrin directly as well as indirectly by eliminating the inhibitory paracrine influence of somatostatin.

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Pirenzepine-sensitive muscarinic receptors regulate gastric somatostatin and gastrin

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1985.248.2.g184 ◽

1985 ◽

Vol 248 (2) ◽

pp. G184-G187 ◽

Cited By ~ 2

Author(s):

R. Sue ◽

M. L. Toomey ◽

A. Todisco ◽

A. H. Soll ◽

T. Yamada

Keyword(s):

Acid Secretion ◽

Muscarinic Receptors ◽

Potent Inhibitor ◽

Competitive Inhibition ◽

Hormone Regulation ◽

Rat Stomach ◽

Response Curves ◽

Gastrin Secretion ◽

Dose Dependent Fashion ◽

Dose Dependent

Pirenzepine, a newly described antagonist of selective muscarinic receptors (M1), has been shown to be a potent inhibitor of acid secretion. To determine whether this property of pirenzepine can be explained in part by its actions on hormones regulating acid secretion, we examined pirenzepine's effects on gastrin and somatostatinlike immunoreactivity (SLI) secretion from the isolated, perfused rat stomach. Carbachol at a dose of 10(-6) M inhibited SLI and stimulated gastrin secretion. Both atropine and pirenzepine reversed these effects in a dose-dependent fashion with D50 values of 1 X 10(-9) and 1 X 10(-7) M, respectively, against gastrin stimulation and 1 X 10(-8) and 1 X 10(-7) M, respectively, against SLI inhibition. Pirenzepine caused a progressive parallel rightward shift in the dose-response curves for SLI inhibition and gastrin stimulation by carbachol, suggesting competitive inhibition. The apparent inhibitory constant (ki) was calculated to be approximately 2 X 10(-9) M. These results indicate that gastrin and SLI release from the stomach is governed by high-affinity muscarinic receptors that are sensitive to pirenzepine. Pirenzepine's action as an acid secretory inhibitor, and possibly as an ulcer therapy drug, may be explained in part by these effects on gastric hormone regulation.

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Stimulation of gastrin and somatostatin secretion from the isolated rat stomach by bombesin

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1981.241.3.g242 ◽

1981 ◽

Vol 241 (3) ◽

pp. G242-G247 ◽

Cited By ~ 4

Author(s):

J. W. DuVal ◽

B. Saffouri ◽

G. C. Weir ◽

J. H. Walsh ◽

A. Arimura ◽

...

Keyword(s):

Maximal Response ◽

Antral Mucosa ◽

Rat Stomach ◽

Peak Period ◽

Cellular Origin ◽

Gastrin Secretion ◽

Somatostatin Secretion ◽

D Cells ◽

Dose Dependent Increase

The role of bombesin in the regulation of gastrin and somatostatin secretion was examined using an isolated vascularly perfused rat stomach preparation. Bombesin caused a biphasic, dose-dependent increase in gastrin and bombesin secretion. Neither somatostatin nor gastrin secretion was inhibited by atropine. The maximal gastrin response to bombesin (198 +/- 75% above basal levels) was less than one-half the maximal response to methacholine (462 +/- 94%). It was postulated that the concomitant release of somatostatin, in part from antral mucosa, attenuated the gastrin response to bombesin; the notion was tested with somatostatin antiserum. A 50- to 100-fold excess of sheep somatostatin antiserum augmented significantly the maximal gastrin response to bombesin by 966% in the initial peak period and by 532% in the plateau period; the response in the plateau period was not significantly different from the maximal response to methacholine. Methacholine stimulated the release of gastric bombesin also, but the exact cellular origin of the peptide could not be ascertained. On the basis of these results and of the topography of antral bombesin neurons and somatostatin D cells, a model for the neural (via bombesin) and paracrine (via somatostatin) control of gastrin secretion within the antrum is proposed.

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The effect of muscarinic and β-adrenergic blockade on cysteamine-induced gastrin secretion by the isolated perfused rat stomach

Life Sciences ◽

10.1016/0024-3205(87)90729-6 ◽

1987 ◽

Vol 41 (13) ◽

pp. 1615-1620 ◽

Cited By ~ 1

Author(s):

C.H.S. McIntosh ◽

V. Bakich ◽

Y.N. Kwok ◽

J.C. Brown

Keyword(s):

Adrenergic Blockade ◽

Rat Stomach ◽

Gastrin Secretion

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Inhibition of neurally mediated gastrin secretion by bombesin antiserum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1985.248.4.g456 ◽

1985 ◽

Vol 248 (4) ◽

pp. G456-G462 ◽

Cited By ~ 5

Author(s):

M. L. Schubert ◽

B. Saffouri ◽

J. H. Walsh ◽

G. M. Makhlouf

Keyword(s):

Electrical Field Stimulation ◽

Nerve Fibers ◽

Rat Stomach ◽

Electrical Field ◽

Gastrin Releasing Peptide ◽

Gastrin Secretion ◽

Somatostatin Secretion ◽

Control Serum ◽

Paracrine Secretion

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.

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Epidermal growth factor-related peptides (EGF-RPs) regulate somatostatin (SST), histamine, and gastrin secretion in human and rat stomach

Gastroenterology ◽

10.1016/s0016-5085(03)82238-2 ◽

2003 ◽

Vol 124 (4) ◽

pp. A443 ◽

Cited By ~ 2

Author(s):

Mitchell L. Schubert ◽

Robert W. McCuen ◽

Stephen L. Settle ◽

Robert J. Coffey

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Rat Stomach ◽

Gastrin Secretion ◽

Epidermal Growth

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Stimulation of gastrin secretion from the perfused rat stomach by somatostatin antiserum

Life Sciences ◽

10.1016/0024-3205(79)90478-8 ◽

1979 ◽

Vol 25 (20) ◽

pp. 1749-1753 ◽

Cited By ~ 105

Author(s):

Bassam Saffouri ◽

Gordon Weir ◽

Khalil Bitar ◽

Gabriel Makhlouf

Keyword(s):

Rat Stomach ◽

Gastrin Secretion ◽

Stimulation Of

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Gastrin and somatostatin secretion by perfused rat stomach: functional linkage of antral peptides

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1980.238.6.g495 ◽

1980 ◽

Vol 238 (6) ◽

pp. G495-G501 ◽

Cited By ~ 7

Author(s):

B. Saffouri ◽

G. C. Weir ◽

K. N. Bitar ◽

G. M. Makhlouf

Keyword(s):

Inverse Relationship ◽

Rat Stomach ◽

Gastrin Secretion ◽

Functional Linkage ◽

Somatostatin Secretion ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Stimulation Of

The isolated vascularly perfused rat stomach was used to study the polarity, kinetics, and stoichiometry of gastrin and somatostatin secretion and the interaction of the two antral peptides. The secretion of gastrin (79%) and somatostatin (95%) was predominantly in the circulation. Methacholine (5 x 10(-8) to 5 x 10(-4) M) produced a biphasic dose-dependent increase in gastrin secretion. The maximal gastrin response (434 +/- 89% above basal levels; P less than 0.001) was partially inhibited by 10(-8) M atropine and completely inhibited by 10(-7) M atropine. Methacholine produced a dose-dependent inhibition of somatostatin secretion; the inhibition was blocked by atropine. An inverse relationship between the secretion of gastrin and somatostatin was noted in the basal state and during infusion of methacholine or prostaglandin E2; the latter had effects on gastrin and somatostatin secretion opposite to those of methacholine. The data, together with data reported elsewhere that somatostatin antiserum stimulates gastrin secretion in the perfused stomach, are consistent with the hypothesis that gastric somatostatin secretion exerts a continuous restraint on basal gastrin secretion and that stimulation of gastrin secretion may be mediated in part by inhibition of somatostatin secretion.

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