Endogenous thyrotropin-releasing hormone (TRH) in the dorsal vagal complex (DVC) is involved in stimulation of hepatic blood flow induced by excitation of raphe pallidus (RPA) in rats

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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Effect of intracisternal thyrotropin-releasing hormone on hepatic blood flow in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.274.2.g277 ◽

1998 ◽

Vol 274 (2) ◽

pp. G277-G282 ◽

Cited By ~ 3

Author(s):

Keisuke Tamori ◽

Masashi Yoneda ◽

Kimihide Nakamura ◽

Isao Makino

Keyword(s):

Central Nervous System ◽

Blood Flow ◽

Nervous System ◽

Hepatic Blood Flow ◽

Cervical Spinal Cord ◽

Hydrogen Gas ◽

Thyrotropin Releasing Hormone ◽

Hydrogen Gas Clearance ◽

Releasing Hormone ◽

The Central Nervous System

Central neuropeptides play a role in many physiological regulatory processes through the autonomic nervous system. Thyrotropin-releasing hormone (TRH) is distributed in the central nervous system and acts as a neurotransmitter to regulate gastric functions through vagal-muscarinic pathways. The central effect of the TRH analog on hepatic blood flow was investigated in urethan-anesthetized rats. Hepatic blood flow was determined by the hydrogen gas clearance technique. Intracisternal injection of the stable TRH analog RX-77368 (5–100 ng) dose dependently increased hepatic blood flow with peak response at 15 min after the peptide was administered (net change from basal for vehicle and 5, 10, 100, and 500 ng RX-77368 was 2.0 ± 0.2, 8.9 ± 0.8, 19.4 ± 2.6, 32.6 ± 3.3, and 28.5 ± 6.8 ml ⋅ min−1 ⋅ 100 g−1, respectively), and this stimulatory effect returned to baseline at 90 min. The stimulation of hepatic blood flow by the intracisternally administered TRH analog was abolished by atropine methyl nitrate (0.15 mg/kg ip), indomethacin (5 mg/kg ip), N G-nitro-l-arginine methyl ester (10 mg/kg iv), and hepatic branch vagotomy but not by cervical spinal cord transection (C6 level). Intravenous injection of RX-77368 did not have any effect on hepatic blood flow. These results indicate that TRH acts in the central nervous system to stimulate hepatic blood flow through vagal-muscarinic and indomethacin- and nitric oxide-dependent pathways.

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