Involvement of threshold level in the contractile responses for some alpha 1-andrenoceptor agonists in the rabbit iris dilators.
1. The relationship between receptor occupancies and contractile responses for some alpha 1-adrenoceptor agonists were investigated in rabbit iris dilator smooth muscles. 2. Noradrenaline acted as a full agonists, 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. The pD2-values of oxymetazoline and xylometazoline were practically equal to the corresponding pKB-values, the negative log of dissociation constant, estimated by the partial irreversible blockade of alpha 1-adrenoceptors with phenoxybenzamine. However, the pD2-values of tizanidine and clonidine were significantly lower than the corresponding pKB-values. 4. The threshold phenomena lay between the receptor occupations and tissue responses, therefore, the pKB-values of partial agonists with lower intrinsic activity were different from their pD2-values. 5. These results suggest that the threshold phenomena in the tissue used may be an important factor in determining the agonist sensitivity.
Konno
F
F
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Takayanagi
I
I
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011817:Rabbits
D000316:Adrenergic alpha-Agonists