Beta3 adrenergic stimulation inhibits the opossum lower esophageal sphincter.
OBJECTIVE
Previous studies have identified adrenergic receptor sites in the lower esophageal sphincter (LES) of animals and humans. A beta3 adrenoceptor has been identified and cloned. The binding site for this receptor has been found in the rat LES in vitro. The aim of the study was to assess the role of a specific beta3 agonist (CL316243) on LES pressure (LESP) in vivo.


METHODS
Anesthetized adult opossums were given CL316243 and isoproterenol intravenously as boluses before and after continuous infusion of L748337 (a specific beta3 antagonist), propranolol, and bethanechol. Blood pressure, heart rate, and LESP were continuously recorded.


RESULTS
CL316243 caused a dose-dependent maximal inhibition of LESP of 88.5% +/- 4.8%. The mean duration of inhibition was 62.2 +/- 9.2 minutes with minimal change in cardiovascular parameters. Isoproterenol caused dose-dependent maximal inhibition of 89.4% +/- 4.7% with mean duration of action of 5.1 +/- 0.9 minutes but was associated with significant hypotension and tachycardia. L748337 and propranolol significantly blocked the effects of CL316243 and isoproterenol, respectively. CL316243 and isoproterenol inhibited the bethanechol-mediated hypertensive LES.


CONCLUSIONS
(1) A selective beta3 agonist, CL316243, caused significant, prolonged, and dose-dependent inhibition of LESP and, unlike isoproterenol, had minimal effect on heart rate and mean arterial pressure. (2) The beta3 antagonist, L748337, selectively inhibited CL316243 without altering the isoproterenol response. (3) CL316243 and isoproterenol both caused inhibition of cholinergic-mediated hypertensive LESP.
Dimarino
Michael
M
Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Banwait
Kuldip
K
Rattan
Satish
S
Cohen
Sidney
S
DiMarino
Anthony J
AJ
D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000627:Aminophenols / Q000494:pharmacology; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004149:Dioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D009893:Opossums; D011312:Pressure; D013449:Sulfonamides / Q000494:pharmacology
D058673:Adrenergic beta-3 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000627:Aminophenols; D004149:Dioxoles; C120576:L 748,337; D013449:Sulfonamides; D018723:Bethanechol; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D007545:Isoproterenol