OPPOSING ROLES FOR D-1 AND D-2 DOPAMINE-RECEPTORS IN THE REGULATION OF LOWER ESOPHAGEAL SPHINCTER MOTILITY IN THE RAT

In the present study we have identified biochemically DA receptors in rat Lower Esophageal Sphincter (LES) and have identified their role in the control of the sphincter motility. Dopamine (DA) both stimulated and inhibited cyclic AMP formation in rat LES; the pharmacological cha racterization of these effects indicated that they were mediated by D- 1 and D-2 receptors, respectively The results obtained with LES helica l strips showed that DA plays both inhibitory and stimulatory effects on the sphincter function, the pharmacological characterization with s elective D-1 and D-2 agonists and antagonists strongly suggested that D-1 receptors are involved in LES contraction, while D-2 receptors med iate the relaxation of the sphincter. The same results were obtained b y measuring intraluminal LES pressure in anesthetized rats. The select ive D-1 agonist fenoldopam (40 mu g/kg, i.v.) increased the LES pressu re; on the other hand bromocriptine (10 mu g/kg, i.v.), which preferen tially interacts with D-2 receptors, induced a decrease of the resting LES pressure.