Intracisternal antisense oligodeoxynucleotides to the thyrotropin-releasing hormone receptor blocked vagal-dependent stimulation of gastric emptying induced by acute cold in rats.
Cold exposure increases TRH gene expression in hypothalamic and raphe nuclei and results in a vagal activation of gastric function. We investigated the role of medullary TRH receptors in cold (4-6 C, 90 min)-induced stimulation of gastric motor function in fasted conscious rats using intracisternal injections of TRH receptor (TRHr) antisense oligodeoxynucleotides (100 microg twice, -48 and -24 h). The gastric emptying of a methyl-cellulose solution was assessed by the phenol red method. TRH (0.1 microg) or the somatostatin subtype 5-preferring analog, BIM-23052 (1 microg), injected intracisternally increased basal gastric emptying by 34% and 47%, respectively. TRHr antisense, which had no effect on basal emptying, blocked TRH action but did not influence that of BIM-23052. Cold exposure increased gastric emptying by 64%, and the response was inhibited by vagotomy, atropine (0.1 mg/kg, i.p.), and TRHr antisense (intracisternally). Saline or mismatched oligodeoxynucleotides, injected intracisternally under similar conditions, did not alter the enhanced gastric emptying induced by cold or intracisternal injection of TRH or BIM-23052. These results indicate that TRH receptor activation in the brain stem mediates acute cold-induced vagal cholinergic stimulation of gastric transit, and that medullary TRH may play a role in the autonomic visceral responses to acute cold.
CURE: Digestive Diseases Research Center, West Los Angeles Veterans Administration Medical Center, and the Department of Medicine, University of California School of Medicine, 90073, USA.
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Martinez
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Wu
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Taché
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002946:Cisterna Magna / Q000502:physiology*; D003080:Cold Temperature; D005746:Gastric Emptying / Q000187:drug effects*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
C114314:BIM 23052; D016376:Oligonucleotides, Antisense; D018025:Receptors, Thyrotropin-Releasing Hormone; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D001285:Atropine