Characterization of postsynaptic alpha1-adrenoceptors in the rabbit iris dilator smooth muscle

Summary Interactions of several alpha-adrenoceptor agonists and antagonists with their receptors were studied in rabbit and guinea pig iris dilator smooth muscle and rabbit aortic strips using pharmacological procedures.In rabbit iris dilators and aortic strips, noradrenaline acted as a full agonist, while oxymetazoline, clonidine and tizanidine acted as partial agonists. The dissociation constants of full and partial agonists in the dilators, calculated after irreversible blockade of a proportion of the active receptors with phenoxybenzamine, were similar to those in the aortic strips. Furthermore, the relative intrinsic efficacies of partial agonists were practically equal in the two tissues, suggesting that these drugs act on the same alpha-adrenoceptors. Since the alpha₂-agonists clonidine and tizanidine had low affinity in the rabbit dilators, the alpha-adrenoceptors in this tissue appear to be of alpha₁-type. These results were further supported by the fact that the pA₂-value of prazosin, an alpha₁-antagonist, was approximately 2 log units higher than that of yohimbine, an alpha₂-antagonist.However, pA₂-values of four quinazolines (prazosin, bunazosin, SM911 and SM2470) and two yohimbine alkaloids (yohimbine and corynanthine) were significantly lower in the rabbit dilator muscle than in rabbit aortic strips. Two imidazoline antagonists (phentolamine and tolazoline) and a phenethanolamine (labetalol) acted on the alpha₁-adrenoceptors in the two tissues nonselectively. These results suggest that alpha₁-adrenoceptors in the rabbit dilator muscle and aortic strips may not be identical and that both selective and nonselective antagonists which act on these receptor sites exist. The pA₂-values of prazosin, SM911 and SM2470 against noradrenaline in guinea pig iris dilator smooth muscle were also significantly lower than those in the rabbit aortic strips, but practically equal to those in the rabbit iris dilators, suggesting that the alpha₁-adrenoceptors in the dilators are the same in these two species.