The contribution of extraneuronal uptake to the trachea-blood vessel selectivity of beta-adrenoceptor stimulants in vitro in guinea-pigs.
1 The potencies relative to isoprenaline of isoetharine, tertiary butyl noradrenaline, salbutamol, orciprenaline, Me 506, rimiterol, fenoterol, carbuterol and terbutaline on isolated preparations of guinea-pig trachea and blood vessels (perfused hind limb) were determined. All the compounds were selective for trachea and selectivity values, i.e. relative potency on trachea divided by relative potency on hind limb, ranged from 2.3 to 21.4. 2 Responses to isoprenaline (the reference compound), tertiary butyl noradrenaline and isoetharine were potentiated on trachea by 50 muM phenoxybenzamine (PHB) and by other inhibitors of extraneuronal uptake (ENU). Under these conditions the selectivity values of all the compounds was close to unity. 3 Selectivity values were also close to unity if they were calculated from data obtained without ENU inhibition, provided that only those compounds not potentiated by PHB on trachea were used. 4 It is proposed that the trachea-blood vessel selectivity shown by beta-adrenoceptor stimulants can be caused by the influence of ENU upon them, rather than by their ability to distinguish between two beta2-adrenoceptors. 5 The suggestion that differences exist between beta2-adrenoceptors in respiratory and vascular smooth muscle is not supported by the in vitro experiments described.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D006168:Guinea Pigs; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D009474:Neurons / Q000378:metabolism*; D009928:Organ Specificity; D010643:Phenoxybenzamine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014132:Trachea / Q000098:blood supply*
D000318:Adrenergic beta-Agonists; D010643:Phenoxybenzamine