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

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.

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

1993 ◽  
Vol 265 (5) ◽  
pp. G880-G886 ◽  
Author(s):  
H. Yang ◽  
G. Ohning ◽  
Y. Tache
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Kainic Acid ◽  
Gastric Fistula ◽  
Dorsal Vagal Complex ◽  
Gastric Function ◽  
Physiological Relevance ◽  
Raphe Pallidus

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.

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

1995 ◽  
Vol 269 (1) ◽  
pp. R1-R6 ◽  
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.

PYY in brain stem nuclei induces vagal stimulation of gastric acid secretion in rats

1995 ◽  
Vol 268 (6) ◽  
pp. G943-G948 ◽  
Author(s):  
H. Yang ◽  
Y. Tache
Keyword(s):  
Acid Secretion ◽  
Brain Stem ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Serotonin Receptor ◽  
Peptide Yy ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Raphe Pallidus ◽  
Stimulation Of

The influence of peptide YY (PYY) microinjected into brain stem nuclei on gastric acid secretion (GAS) was investigated in urethan-anesthetized rats with gastric cannula. PYY (30-200 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) induces a dose-related and vagal-dependent stimulation of GAS (net increase from 13 +/- 4 to 59 +/- 12 mumol/90 min). PYY (200 ng) injected intravenously intracisternally into sites adjacent to the DMN had no effect. GAS induced by PYY into the DMN was potentiated by coinjection of thyrotropin-releasing hormone (TRH, 30 ng) or the serotonin receptor (5-HT2) agonist (+/-)-1-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (357 ng) and by microinjection of kainic acid (1 ng) into the raphe pallidus. Prepro-TRH-(160-169) (200 ng into the DMN) did not influence the stimulatory effect of PYY. PYY (200 ng) microinjected into the raphe pallidus, raphe obscurus, and nucleus ambiguous also increased GAS, although the response was of shorter duration than that in the DMN. These results indicate that PYY acts in brain stem nuclei involved in the vagal regulation of GAS and that PYY action in the DMN is potentiated by TRH or 5-HT2 receptor agonist acting at this site.

TRH analogue, RX 77368, injected into dorsal vagal complex stimulates gastric secretion in rats

1988 ◽  
Vol 254 (5) ◽  
pp. G639-G643 ◽  
Author(s):  
R. L. Stephens ◽  
T. Ishikawa ◽  
H. Weiner ◽  
D. Novin ◽  
Y. Tache
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Nucleus Tractus Solitarius ◽  
Acid Output ◽  
Medial Longitudinal Fasciculus ◽  
Dorsal Vagal Complex ◽  
High Concentration ◽  
Reticular Nuclei ◽  
Stimulation Of

Medullary sites inducing gastric acid secretion in response to microinjection of the stable analogue of thyrotropin-releasing hormone (TRH; RX 77368, pGlu-His-[3,3'-dimethyl]-Pro-NH2) were investigated in urethan-anesthetized rats. Gastric acid output was recorded every 2 min through a double gastric cannula constantly perfused with 0.9% saline solution maintained at pH 5.5 using an automatic titrator. Unilateral microinjection of RX 77368 (10-100 ng in 50-nl volume) into the dorsal vagal complex (DVC), the dorsal vagal nucleus and nucleus tractus solitarius, induced a significant dose-dependent stimulation of gastric acid secretion. The peak response occurred within 50 min and lasted over 1 h. Other medullary sites, including the lateral, dorsal, and parvocellular reticular nuclei; the medial longitudinal fasciculus; and the medial cuneate nucleus injected with RX 77368 (10-100 ng), were inactive. The TRH metabolites, TRH-OH and His-Pro diketopiperazine (100 ng), injected into the DVC did not influence gastric acid secretion. The stimulation of gastric acid secretion induced by DVC injection of TRH was abolished by vagotomy. These results demonstrate that 1) the DVC is an important site of action for TRH-induced stimulation of gastric acid secretion, 2) TRH action in the DVC is not secondary to the formation of TRH metabolites, and 3) the effect is expressed by vagal efferent pathways. These findings added to the high concentration of TRH-immunoreactivity and receptors in the DVC suggest a role for endogenous TRH in the regulation of vagal outflow to the stomach.

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