Abstract
The relative potency of α-adrenoceptor agonists and the dissociation constants of competitive antagonists were studied to characterize the post junctional α-adrenoceptor of the human iris dilator muscle. The data obtained from human iris dilator tissue was compared to that from rabbit. The iris dilator muscle was mounted in an organ bath and tension changes were recorded. (−)-Norepinephrine, (−)-phenylephrine (PE), oxymetazoline and p-aminoclonidine caused contractile responses in albino rabbit, pigmented rabbit and human iris dilator muscle in a concentration-dependent manner. The imidazoline molecules were partial agonists. In rabbit iris dilator, desensitization occurred to repeated oxymetazoline application at an interval of 1 h but recovery to the agonist activity was complete in about 3 h. Exposure to cocaine (10 μmol/l), hydrocortisone (100 μmol/l) and U-0521, a catechol-O-methyltransferase inhibitor (100 pmol/l), significantly potentiated the response to norepinephrine by 92-, 32- and 7 fold in iris dilator tissue of albino rabbit, pigmented rabbit and human, respectively. After block of “uptake1” and “uptake2”, the EC50 values of norepinephrine in the albino rabbit, pigmented rabbit and human iris dilator did not differ and ranged from 99 to 195 nmol/l. Small but significant potentiation by uptake blockers was also observed in the responses to PE in the albino rabbit or pigmented rabbit iris dilator. The average maximum tension induced by 100 μmol/l PE was 96 ± 11 mg (n = 10), 197 ± 11 mg (n = 11), 45 ± 5 mg (n = 27) in albino rabbit, pigmented rabbit and human iris dilator, respectively.
In human iris dilator, the responses to PE were competitively antagonized by prazosin, 5-methylurapidil and phentolamine with apparent pKB values of 7.3, 6.6 and 7.5, respectively. The pK B values of the prazosin-PE interaction in iris dilator of albino and pigmented rabbit were 8.6 and 6.4, respectively.
These results suggest that the post-junctional α-adrenoceptors in iris dilator may be similar to that in pigmented rabbit iris. The α-adrenoceptor of the human or pigmented rabbit iris dilator may be characterized as α1L-adrenoceptor subtype. The α-adrenoceptor of albino rabbit iris dilator appears to be a high affinity subtype.
Furthermore, albino rabbit may not be the best strain for the drug research which is relevant to human ocular therapeutics.
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Ishikawa, H., Patil, P.N. & Miller, D.D. Comparison of post-junctional α-adrenoceptors in iris dilator muscle of humans, and albino and pigmented rabbits. Naunyn-Schmiedeberg's Arch Pharmacol 354, 765–772 (1996). https://doi.org/10.1007/BF00166903
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DOI: https://doi.org/10.1007/BF00166903