Medullary TRH is involved in gastric protection induced by low dose of kainic acid into the raphe pallidus

1995 ◽  
Vol 268 (4) ◽  
pp. G548-G552 ◽  
Author(s):  
H. Kaneko ◽  
H. Yang ◽  
G. Ohning ◽  
Y. Tache

The gastroprotective effect of kainic acid microinjected into the raphe pallidus (Rpa) at a dose subthreshold to increase acid secretion was investigated in urethan-anesthetized rats. Kainic acid (25 pg/30 nl) microinjected into the Rpa inhibited by 65.8% gastric damage induced by intragastric ethanol (60%). No protection was observed when kainic acid was injected outside of the Rpa. The cytoprotective effect was completely abolished by thyrotropin-releasing hormone (TRH) antibody microinjected bilaterally (1.3 micrograms/site) into the dorsal motor nucleus of the vagus (DMN), indomethacin (5 mg/kg ip), and atropine (0.3 mg/kg sc). Microinjection of TRH antibody outside of the DMN or of control antibody into the DMN did not modify the protective action induced by kainic acid into the Rpa. The TRH antibody microinjected alone into the DMN did not alter the severity of the ethanol-induced gastric lesions. These data indicate that excitation of Rpa neurons by a low dose of kainic acid results in cytoprotection against ethanol lesions. Furthermore, this cytoprotection occurs as a result of TRH action in the DMN and activation of muscarinic and prostaglandin pathways.

1991 ◽  
Vol 260 (1) ◽  
pp. G91-G96 ◽  
Author(s):  
R. L. White ◽  
C. D. Rossiter ◽  
P. J. Hornby ◽  
J. W. Harmon ◽  
D. K. Kasbekar ◽  
...  

The nucleus raphe obscurus (NRO) has recently emerged as an important nucleus for excitation of gastric motor activity through projections to the dorsal motor nucleus of the vagus (DMV) [P. J. Hornby, C. D. Rossiter, R. L. White, W. P. Norman, D. H. Kuhn, and R. A. Gillis. Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G91-G96, 1990; and M. J. McCann, G. E. Herman, and R. C. Rogers. Brain Res. 486: 181-184, 1989]. A neurotransmitter thought to be involved in this NRO-DMV pathway is thyrotropin-releasing hormone (TRH), a peptide that excites gastric activity when microinjected into the DMV. The purpose of the present study was to determine whether gastric acid and pepsin secretion were altered by 1) activation of neurons in the NRO by microinjection of kainic cid and 2) microinjection of TRH into the DMV in chloralose-anesthetized cats. Microinjection of kainic acid into the NRO increased gastric acid secretion [baseline was 6 +/- 2 (mu eq) H+/15 min (n = 7) and increased to 8 +/- 2, 26 +/- 11 (P less than 0.05), and 21 +/- 7 mu eq/15 min (P less than 0.05) during the first, second, and third 15-min periods after microinjection, respectively]. Pepsin output also increased from a baseline of 287 +/- 67 pepsin units (PU) (n = 4) to 507 +/- 126 PU 15 min postinjection, 541 +/- 118 PU 30 min after injection (P less than 0.05), 608 +/- 92 PU 45 min after injection (P less than 0.05), and 700 +/- 156 PU 60 min postinjection (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


1995 ◽  
Vol 268 (6) ◽  
pp. G943-G948 ◽  
Author(s):  
H. Yang ◽  
Y. Tache

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.


1989 ◽  
Vol 24 (sup162) ◽  
pp. 15-18 ◽  
Author(s):  
T. Okumura ◽  
K. Okamura ◽  
S. Kitamori ◽  
H. Hara ◽  
Y. Shibata ◽  
...  

1995 ◽  
Vol 269 (1) ◽  
pp. R1-R6 ◽  
Author(s):  
M. Yoneda ◽  
Y. Tache

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.


1998 ◽  
Vol 275 (5) ◽  
pp. G1056-G1062 ◽  
Author(s):  
Hiroshi Kaneko ◽  
Jonathan Kaunitz ◽  
Yvette Taché

Peripheral mechanisms involved in kainic acid injected into the raphe pallidus (Rpa)-induced gastric protection were investigated in urethan-anesthetized rats. Gastric mucosal blood flow (GMBF), acid secretion, and gastric injury induced by intragastric ethanol (60%) were measured in response to kainic acid (25 pg) injected into the Rpa. Kainic acid reduced ethanol-induced gastric lesions by 57%. The protective effect was blocked by vagotomy, capsaicin deafferentation, and intravenous injection of the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8—37) and NG-nitro-l-arginine methyl ester (l-NAME).l- but notd-arginine reversed thel-NAME action. Kainic acid injected into the Rpa, unlike outside sites, increased basal GMBF but not acid secretion. Indomethacin unmasked an acid secretory response to kainic acid. These results show that kainic acid injected into the Rpa at a dose that did not stimulate acid secretion, due to the inhibitory effect of prostaglandins, protects against ethanol-induced gastric injury through vagal-dependent activation of CGRP contained in capsaicin-sensitive afferents and nitric oxide-mediated gastric vasodilatory mechanisms.


2003 ◽  
Vol 46 (3) ◽  
pp. 355-360 ◽  
Author(s):  
Cristina Setim Freitas ◽  
Maria Fernanda Rodrigues de Paula ◽  
Lia Rieck ◽  
Maria Consuelo Andrade Marques

The plants that compound the Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of a crude hydroalcoholic extract of Pfaffia sp on the gastrointestinal tract. Female Wistar rats were pretreated orally (p.o.) with the hydroalcoholic extract of Pfaffia (0.5, 1 and 2 g.kg-1) before the induction of ulcer with hypothermic restraint stress (HRS), ethanol (ET) or indomethacin (IND). Control animals received water (C) or ranitidine (60mg/kg) p.o. The hydroalcoholic extract of Pfaffia (0.5, 1 and 2 mg.kg-1) protected rats against HRS and ET - induced ulcers, but was not able to protect the gastric mucosa against IND - induced ulcers. When injected into the duodenal lumen, the hydroalcoholic extract of Pfaffia inhibited basal and stimulated acid secretion in pylorus-ligated rats. These results indicate that this plant has a protective action against gastric lesions of the mucosa involving the reduction of gastric acid secretion.


1999 ◽  
Vol 127 (7) ◽  
pp. 1603-1610 ◽  
Author(s):  
Belén Beltrán ◽  
Ma Dolores Barrachina ◽  
Asunción Méndez ◽  
Enrique Quintero ◽  
Juan V Esplugues

1995 ◽  
Vol 269 (6) ◽  
pp. R1301-R1307
Author(s):  
K. Kato ◽  
H. Yang ◽  
Y. Tache

Mechanisms involved in central thyrotropin-releasing hormone (TRH) analogue RX-77368-induced prevention of gastric lesions were investigated in urethan-anesthetized rats. Gastric lesions were induced by intragastric administration of ethanol (4 ml/kg) and assessed 1 h later by macroscopic visualization using computerized image analysis. RX-77368 (3, 5, and 10 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) decreased ethanol-induced gastric lesions by 79, 68, and 61%, respectively. RX-77368 at 1.5, 15, or 30 ng into the DMN or at 3 or 10 ng into the nucleus of the solitary tract, hypoglossal nucleus, or reticular field was ineffective in preventing mucosal damage. The protective effect of RX-77368 (3 ng into the DMN) was partly inhibited by peripheral injection of indomethacin and completely blocked by atropine, the calcitonin gene-related peptide antagonist, CGRP-(8-37), and NG-nitro-L-arginine methyl ester (L-NAME). L-arginine, but not D-arginine, reversed the effect of L-NAME. RX-77368 (3 ng into the DMN) enhanced gastric prostaglandin E2 (PGE2) release. These data indicate that low doses of TRH analogue act in the DMN to induce gastric protection against ethanol injury through muscarinic-, PGE2-, CGRP-, and nitric oxide-dependent mechanisms.


1993 ◽  
Vol 265 (5) ◽  
pp. G880-G886 ◽  
Author(s):  
H. Yang ◽  
G. Ohning ◽  
Y. Tache

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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