Effects of pGlu-His-Pro-amphetamine (TRH-amphetamine) on the isolated duodenum of the guinea-pig: antagonistic effect of amphetamine on TRH response

Abstract

pGlu-His-Pro-dexamphetamine (TRH-A) produced a contraction through the release of acetylcholine from postganglionic cholinergic neurons in the duodenum of the guinea-pig in the same manner as TRH. However, the affinity of TRH-A (pD2, 4.70) toward isolated duodenum was one thousandth that of TRH (pD2, 7.74). The effects of TRH-A (10(-4)M) were abolished by 10(-7) M TRH, but only partially (about 50%) inhibited by 10(-4) M d-amphetamine. D-Amphetamine showed no stimulatory effect on the myenteric nerves. However, the duodenal response to TRH (10(-6) M) was dose dependently inhibited by d-amphetamine (10(-6), 10(-5), 10(-4) M) while the phasic and tonic contractions caused by high K+ (40 mM) or the contractile responses to acetylcholine (10(-7) M) were not blocked by d-amphetamine. These results indicate that d-amphetamine may act as an antagonist to TRH without influencing the movement of calcium ions in smooth muscle or muscarinic receptors and that contractile responses to TRH-A are mediated through TRH receptors in the myenteric cholinergic nerves.