TRH in dorsal vagal complex mediates acid response to excitation of raphe pallidus neurons in rats

The role of thyrotropin-releasing hormone (TRH) in the dorsal vagal complex (DVC) in the acid response to excitation of raphe pallidus neurons was investigated in urethan-anesthetized rats with gastric fistula. Kainic acid (0.19 microgram/30 nl) microinjected into the raphe pallidus stimulated gastric acid secretion. The response was prevented by vagotomy. A specific polyclonal TRH antibody, 8964, was raised and characterized (50% inhibitory dose for TRH was 80 pg/ml at an antibody final dilution of 1:10(5)). The TRH antibody injected intracisternally blocked the acid response to intracisternal TRH, but not that of the TRH analogue RX-77368. The TRH antibody (0.33, 0.65, or 1.3 micrograms.100 nl-1.site-1) microinjected bilaterally into the DVC prevented dose dependently by 31, 60, and 76%, respectively, the increase in acid secretion induced by kainic acid injected into the raphe pallidus. The TRH antibody (1.3 microgram/site) microinjected into medullary sites outside of the DVC had no effect. These data indicate that excitation of raphe pallidus neurons induces a vagal-dependent stimulation of gastric acid secretion that is mediated by endogenous TRH in the DVC. TRH neurons in the raphe pallidus projecting to the DVC may have a physiological relevance in the vagal regulation of gastric function.

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Serotonin enhances gastric acid response to TRH analogue in dorsal vagal complex through 5-HT2 receptors in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.269.1.r1 ◽

1995 ◽

Vol 269 (1) ◽

pp. R1-R6 ◽

Cited By ~ 4

Author(s):

M. Yoneda ◽

Y. Tache

Keyword(s):

Acid Secretion ◽

Receptor Antagonist ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Kainic Acid ◽

Thyrotropin Releasing Hormone ◽

Dorsal Vagal Complex ◽

Releasing Hormone ◽

Anesthetized Rats ◽

Raphe Pallidus

The effect of serotonin (5-HT) and thyrotropin-releasing hormone (TRH) analogue, p-Glu-His-[3,3'-dimethyl]-Pro-NH2 (RX-77368), injected into the dorsal vagal complex (DVC) on gastric acid secretion was assessed in urethan-anesthetized rats with gastric cannula. 5-HT (0.1, 0.2, 1, or 10 nmol into the DVC) enhanced the acid response to RX-77368 (25 pmol, DVC) by 54, 100, 147, and 144%, respectively, whereas 5-HT given alone had no effect. The 5-HT2 receptor agonists (1 nmol, DVC), ( +/- )-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride, 1-(alpha, alpha, alpha-trifluoro-m-tolyl)-piperazine hydrochloride, and alpha-methyl-5-HT increased the gastric acid response to coinjection of RX-77368 (25 pmol) by 153, 108, and 96%, respectively, whereas 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A), 7-trifluoromethyl-4(4-methyl-1-piperazinyl)- pyrrolo[1,2-a]quinoxaline (5-HT1A/1B), and 3-(2-aminoethyl)-2-methyl-1-H-indol-5-ol hydrochloride hydrate (2-methyl-5-HT3) did not. The 5-HT2 receptor antagonist, 3-[2-(4-fluorobenzoyl)-1-piperdinyl]ethyl]-2,4(1H,3H)-quinazoli nedone tartrate (ketanserin; 20 nmol), injected intracisternally abolished the potentiating action of 5-HT injected into the DVC with RX-77368, whereas the 5-HT antagonists 8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4,5]- decan-4-one (spiperone; 5-HT2/1A) and 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1- yl)methyl]-4H-carbazol-4-one hydrochloride dihydrate (ondansetron; 5-HT3) did not. Ketanserin (1 nmol/site bilaterally into the DVC) decreased the acid response to kainic acid injected into the raphe pallidus by 62%. These data suggest that 5-HT acting at 5-HT2 receptors in the DVC potentiates the gastric acid response to exogenous and endogenous TRH.

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Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.272.5.g987 ◽

1997 ◽

Vol 272 (5) ◽

pp. G987-G993

Author(s):

H. Yang ◽

Y. Tache

Keyword(s):

Substance P ◽

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Kainic Acid ◽

Dorsal Vagal Complex ◽

Neurokinin 1 ◽

Raphe Pallidus ◽

Gas Response ◽

Stimulation Of

Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.

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Role of pancreatic polypeptide in canine gastric acid secretion.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1979.236.4.e488 ◽

1979 ◽

Vol 236 (4) ◽

pp. E488 ◽

Cited By ~ 1

Author(s):

D L Parks ◽

R L Gingerich ◽

B M Jaffe ◽

B Akande

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Significant Role ◽

Pancreatic Polypeptide ◽

Gastric Fistula ◽

Background Infusion ◽

Duodenal Acidification ◽

Acid Release

The interrelationships of canine pancreatic polypeptide (cPP) and gastric acid secretion were studied in dogs following infusion of histamine or pentagastrin. Pentagastrin stimulated gastric acid release 30-fold and simultaneously increased plasma cPP secretion by an average of 120 pg/ml. Although histamine stimulated gastric acid secretion to a comparable degree, it had no effect on plasma cPP levels. Three mechanisms of inhibition of acid secretion (cimetidine, duodenal acidification, and somatostatin) had different effects on pancreatic polypeptide (PP) levels. With a background infusion of pentagastrin, cimetidine did not affect cPP levels. In contrast, somatostatin dramatically inhibited both gastric fistula output and cPP release. Finally, a 10-min duodenal irrigation with 0.1 N HCl resulted in a brief spike in cPP levels (from 266 +/- 12 to 347 +/- 31 pg/ml) at the time of greatest inhibition of histamine-stimulated acid secretion. Infusions of histamine + porcine pancreatic polypeptide (pPP) at concentrations of 1.0 and 2.25 microgram/kg per h and of pentagastrin + pPP at 2.25 microgram/kg per h closely simulated postprandial cPP levels (mean 1306 +/- 18 pg/ml at 30 min) but produced no change in gastric fistula output. These studies demonstrated that PP levels and rates of gastric acid secretion are unrelated and that at physiologic concentrations PP plays no significant role in the regulation of gastric acid secretion.

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