Persistent beta-adrenoceptor blockade with alkylating pindolol (BIM) in guinea-pig left atria and trachea.
The actions of alkylating pindolol (N8-bromoacetyl-N1-3'-(4-indolyloxy)-2'-hydroxypropyl[z]-1,8- diamino-p-menthane; BIM) have been examined on beta-adrenoceptors in guinea-pig left atria and trachea. In organ bath experiments, addition of BIM (greater than or equal to 0.1 microM), followed by washout, produced concentration-dependent rightward shifts of the dose-response curve to cumulative additions of (-)-isoprenaline and oxymethylene-isoprenaline and reductions in the maximal response. The "apparent" pA2 value for BIM was 9.23 +/- 0.20 (slope = 0.98 +/- 0.20). Changes in the maximal density of beta-adrenoceptor binding sites were determined in guinea-pig left atrial membranes using [125I]-cyanopindolol. BIM (0.1, 1.0 and 10 microM) produced 14, 23 and 41% reductions in Bmax with no change in KD. The binding of [125I]-BIM to guinea-pig left atrial membranes had a high non-specific binding component and a pseudo-Hill coefficient less than unity. The "apparent" KD value of [125I]-BIM at beta-adrenoceptor binding sites was 85.7 +/- 57.9 pM.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000081005:Cyclohexane Monoterpenes; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000081005:Cyclohexane Monoterpenes; D011943:Receptors, Adrenergic, beta; C057316:N(8)-bromoacetyl-N(1)-3'-(4-indolyloxy)-2'-hydroxypropyl-1,8-diamino-4-menthane; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol