The beta-adrenoceptor selectivity profile of BRL 37344 in the pithed rat.
1. Rats were pithed in order to disrupt baroreflex pathways. Heart rate was used as a measure of beta 1-adrenoceptor activity, blood pressure as a measure of beta 2-adrenoceptor activity and oxygen consumption and brown adipose tissue temperature as measures of beta 3-adrenoceptor activity. 2. The effects of the selective beta 3-adrenoceptor agonist BRL 37344 were compared with those of isoprenaline, a non-selective beta-adrenoceptor agonist, and denopamine and salbutamol, which are respectively beta 1 and beta 2-adrenoceptor agonists. 3. Denopamine was 10-fold more potent on heart rate than blood pressure, whilst salbutamol was 18-fold more potent on blood pressure than heart rate. These findings confirm that in this preparation increases in heart rate are predominantly beta 1 adrenoceptor-mediated, whilst blood pressure is beta 2-adrenoceptor-mediated. Further confirmation is provided by the blockade with atenolol, of the chronotropic effect, but not the blood pressure effect, of isoprenaline. 4. BRL 37344 was the most potent beta-adrenoceptor agonist on both oxygen consumption and brown adipose tissue temperature, revealing the beta 3-nature of these responses. Dose-response curves for oxygen consumption and brown adipose tissue temperature were identical, whichever of the beta-adrenoceptor agonists was used. Both systems may be considered equally effective as indicators of beta 3-adrenoceptor agonist activity.
Oriowo
M A
MA
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, Philadelphia.
Sennitt
M V
MV
Smith
S A
SA
Ruffolo
R R
RR
Cawthorne
M A
MA
D000273:Adipose Tissue / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate; D007545:Isoproterenol / Q000494:pharmacology; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; C057368:BRL 37344; D007545:Isoproterenol