Comparative effects of various centrally acting gastric secretagogues including PCPGABA and TRH in the perfused rat stomach preparation

Abstract

The effects of 2-(p-chlorophenyl)-GABA (PCPGABA), thyrotropine releasing hormone (TRH), insulin and 2-deoxy-D-glucose (2DG) on gastric acid secretion, vagal nerve efferent activity and blood glucose level were. examined in anesthetized rats. The latencies of onset of hypersecretion were 10 min for TRH (1 μg/rat, i.c.), 20 min for PCPGABA (4 mg/kg, s.c.), 60 min for 2DG (200 mg/kg, i.v.) and 90 min for insulin (2 U/kg, i.v.), respectively. The secretagogue actions of PCPGABA and TRH were more potent than those of 2DG and insulin. All these secretagogues caused the efferent activation of the cervical vagal transmission, and the latencies for these vagal activation were shorter than those seen in gastric acid hypersecretion. Atropine and vagotomy completely abolished the secretagogue actions of these stimulants. PCPGABA and TRH were ineffective on the blood glucose level, unlike insulin and 2DG. These results suggest that PCPGABA, TRH, 2DG and insulin stimulate gastric acid secretion via central vagal cholinergic pathways, even though the precise mechanisms for each stimulant seem to be different.