The actions of some beta-receptor agonists and xanthines on isolated muscle strips from the human oesophago-gastric junction.
Isolated preparations from the circular muscle layer of the human oesophago-gastric junction were mounted in organ baths and isometric tension recorded. During an equilibration period, active resting tension developed suggesting that the preparations were representing the lower oesophageal sphincter. Active tension was abolished by exposing the preparations to Ca(++)-free medium. The two xanthines theophylline and enprofylline almost equipotently relaxed the preparations in a concentration-dependent manner (10(-7)-10(-3) M). Within therapeutic concentrations, theophylline inhibited active resting tension by 30-60%, while enprofylline lowered tension by less than 20%. Inhibitory actions of adenosine were demonstrated, and this suggests that adenosine antagonism is not the mechanism of action for xanthines in the oesophagus. Non-selective beta-receptor stimulation with isoprenaline inhibited active tension by 70% (10(-7) M), while beta 2-receptor stimulation with terbutaline inhibited tension by 47% (10(-5) M). Dobutamine, believed to preferentially stimulate beta 1-receptors, inhibited active tension in a concentration-dependent manner (10(-7)-10(-4) M). Metoprolol (10(-6) M), a selective beta 1-receptor antagonist, shifted the concentration-response curve for isoprenaline to the right, but left the maximal response unchanged. It is concluded that xanthines and beta-receptor agonists have inhibitory actions on circular muscle from the human oesophagogastric junction. The experimental data suggest the presence of beta 1- as well as beta 2-receptors, both mediating inhibition of active resting tension.
Tøttrup
A
A
Department of Surgical Gastroenterology L, Aarhus Municipal Hospital, Denmark.
Forman
A
A
Madsen
G
G
Andersson
K E
KE
D000241:Adenosine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013779:Tetrodotoxin / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D014970:Xanthines; D004280:Dobutamine; D013779:Tetrodotoxin; D008790:Metoprolol; D000241:Adenosine; D007545:Isoproterenol