Effects of bromoacetylalprenololmenthane (BAAM), an irreversible beta-adrenoceptor antagonist, on the rat isolated left atria and portal vein.
1. The effects of treatment with bromoacetylalprenololmenthane (BAAM), an irreversible beta-adrenoceptor antagonist, for 30 min on the contractile responses of the rat left atria and portal vein have been determined. 2. On the electrically driven rat left atria, BAAM at 10(-5) M followed by a 60-min wash-out caused parallel rightward shifts of the isoprenaline response curves with no reduction in the maximal response to isoprenaline. 3. Treatment of the atria with BAAM at 3 x 10(-5) M caused non-parallel rightward shifts of isoprenaline response curves with a reduction in the maximum response to isoprenaline. The KA (dissociation constant) for isoprenaline at beta 1-adrenoceptors was 7.3 x 10(-7) M. Calculation of receptor occupancy demonstrated that in order to produce a maximal response of the rat left atria, isoprenaline had to occupy 12% of the beta 1-adrenoceptors. 4. Treatment of the atria with higher concentrations of BAAM (greater than or equal to 6 x 10(-5) M) caused a non-specific action, the reduction of the response to electrical stimulation. 5. On the rat portal vein, BAAM at 3 x 10(-7)-3 x 10(-6) M followed by a 45-min wash-out had no effect on the spontaneous contractile activity, caused non-parallel rightward shifts of isoprenaline response curves with a depression of the isoprenaline maximum responses. Using data derived from experiments with 3 x 10(-7), 10(-6) and 3 x 10(-6) M BAAM, the KA for isoprenaline at beta 2-adrenoceptor was 6.4, 3.7 and 7.7 x 10(-7) M and the calculated receptor occupancy was that in order to produce a maximal response of the rat portal vein, isoprenaline had to occupy 14, 21 and 12%, respectively of the beta 2-adrenoceptors. 6. The present study with the rat left atria and portal vein has shown that it is possible to determine treatments with BAAM that produce no non-specific actions and consequently BAAM may be used as an experimental tool in KA and receptor occupancy determinations in these tissues.
Doggrell
S A
SA
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects* / Q000294:innervation; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; C045331:bromoacetylalprenololmenthane; D000526:Alprenolol; D007545:Isoproterenol