Involvement of threshold level in the contractile responses for some α1-adrenoceptor agonists in the rabbit iris dilators

Abstract

1. 1. The relationship between receptor occupancies and contractile responses for some α 1-adrenoceptor agonists were investigated in rabbit iris dilator smooth muscles. 2. 2. Noradrenaline acted as a full agonist, while oxymetazoline and xylometazoline behaved as partial agonists with moderately higher intrinsic activity, and tizanidine and clonidine were partial agonists with lower intrinsic activity. 3. 3. The pD 2-values of oxymetazoline and xylometazoline were practically equal to the corresponding pK B-values, the negative log of dissociation constant, estimated by the partial irreversible blockade of α 1-adrenoceptors with phenoxybenzamine. However, the pD 2-values of tizanidine and clonidine were significantly lower than the corresponding pK B- values . 4. 4. The threshold phenomena lay between the receptor occupations and tissue responses, therefore, the pK B- values of partial agonists with lower intrinsic activity were different from their pD 2-values. 5. 5. These results suggest that the threshold phenomena in the tissue used may be an important factor in determining the agonist sensitivity.