The Adrenergic Control of Lower Esophageal Sphincter Function: Response to Beta2 Adrenergic Agonists

Abstract

Lands and co-workers have demonstrated a significant degree of selectivity of action at the beta adrenergic receptors of different tissues (1-3). Two types of beta adrenergic receptors, beta1 and beta2, have been proposed. Beta adrenergic effects on the heart are mediated by beta: receptors while the effects on bronchial and vascular smooth muscle are mediated by beta2 receptors (4-6). Although several selective beta2 adrenergic agonists have been synthesized, there is little information on the nature of the beta adrenergic receptors of the gastrointestinal tract. We have recently demonstrated that the lower esophageal sphincter (LES) of the opossum, an animal with a smooth-muscle distal esophagus similar to man, showed a dose-related inhibitory response to beta adrenergic stimulation (7). The purpose of this study was to compare the LES inhibitory response of iso-proterenol, a beta adrenergic agonist with effects at both types of beta receptors, with the selective beta2 adrenergic agonists, salbutamol and carbuterol. Our aim is to determine whether a beta2 adrenergic agonist can be used to reduce basal LES pressure without significantly altering the blood pressure or heart rate. Methods. All studies were performed on the adult opossum, species Didelphis vir-giniana. Male and female animals weighing between 2.2 and 4.6 kg were anesthetized with 2.0% chloralose (3.0 cm3/kg). After successful anesthesia, a heparinized cannula was inserted into the femoral artery and connected to an external transducer (Statham Instruments, Inc., Oxnard, CA) for constant blood pressure monitoring. A similar cannula was inserted into the opposite femoral vein for drug administration. Patency of this cannula was maintained through a slow infusion of 0.9 % saline. Intraluminal pressures were measured through water-filled polyvinyl catheters, 1.4 mm i.d., connected to external transducers (Statham P23BB) with a linear external calibration of 0-250 mmHg.