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 TRK gene expression in hypothalamic and raphe nuclei and results in a vagal activation of gastric function. We inves tigated the role of medullary TRH receptors in cold (4-6 C, 90 min)-in duced stimulation of gastric motor function in fasted conscious rats u sing intracisternal injections of TRH receptor (TRHr) antisense oligod eoxynucleotides (100 mu g twice, -48 and - 24 h). The gastric emptying of a methyl-cellulose solution was assessed by the phenol red method. TRH (0.1 mu g) or the somatostatin subtype 5-preferring analog, BIM-2 3052 (1 mu g), injected intracisternally increased basal gastric empty ing by 34% and 47%, respectively. TRHr antisense, which had no effect on basal emptying, blocked TRH action but did not influence that of BI M-23052. Cold exposure increased gastric emptying by 64%, and the resp onse was inhibited by vagotomy, atropine (0.1 mg/kg, ip), and TRHr ant isense (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 activat ion in the brain stem mediates acute cold-induced vagal cholinergic st imulation of gastric transit, and that medullary TRH may play a role i n the autonomic visceral responses to acute cold.