Beta 3-adrenoceptors mediating relaxation of the oesophageal tunica muscularis mucosae and distal colon in the rat: comparative pharmacology and their desensitization by BRL 37344.
1. In the rat isolated distal colon and oesophagus, relaxant responses to (-)-isoprenaline were poorly antagonized by propranolol (0.1 microM), suggesting an involvement of beta 3-adrenoceptors. 2. In the presence of propranolol the rank order of potency for the agonist-induced relaxations was similar in the two tissues. 3. BRL 37344 was a partial agonist relative to isoprenaline in the colon but when a single maximal concentration of BRL 37344 (1 microM) was added, a full relaxation was observed. 4. BRL 37344 desensitized responses to isoprenaline in both the colon and oesophagus. 5. (+/-)-Cyanopindolol (1.0 microM) antagonized the relaxatory responses to both isoprenaline and BRL 37344 in the distal colon and oesophagus and reduced the desensitizing effect of BRL 37344. 6. The present study demonstrates that the beta-adrenoceptors mediating relaxation in both the rat isolated distal colon and oesophagus are of the beta 3-adrenoceptor subtype. Desensitization appears to result from the binding of BRL 37344 to the beta 3-adrenoceptor in a manner which is blockable by cyanopindolol.
Kelly
J
J
Smithkline Beecham Pharmaceuticals, Welwyn, Hertfordshire, UK.
Houston
G
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D004983:Ethanolamines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C047975:cyanopindolol; C057368:BRL 37344; D011433:Propranolol; D010869:Pindolol; D007545:Isoproterenol