Article date: July 1999
By: Seigo Nakamura, Takanobu Taniguchi, Fumiko Suzuki, Yoshio Akagi, Ikunobu Muramatsu, in Volume 127, Issue 6, pages 1367-1374
Subtypes of α1‐adrenoceptor in rabbit iris have been examined in functional, binding and molecular biological experiments.
In functional studies, exogenous and endogenous noradrenaline produced contractions of the iris dilator muscle. The contractile responses to noradrenaline were competitively antagonized by a range of α1‐adrenoceptor antagonists (pA2 values): prazosin (8.1), WB4101 (8.2), BMY7378 (5.9), YM617 (9.5), JTH‐601 (8.8), HV723 (7.8) and KMD‐3213 (9.8). The same order of inhibitory potency was seen in the adrenergic responses to electrical stimulation. This affinity profile corresponds well to that of the putative α1L‐adrenoceptor, which has been proposed in lower urinary tract tissues.
In binding studies on rabbit iris membrane however, prazosin, KMD‐3213 and WB4101 displayed high affinity (pKd or pKi: 9.6, 10.3, 9.6, respectively), and BMY7378 displayed low affinity (pKi: 6.9). These results show that the binding sites typically correspond to α1A‐adrenoceptor subtype in character, and we could not detect the significant amount of α1L‐adrenoceptor subtype.
The expression of the three distinct mRNAs that encode proteins of α1a‐, α1b‐ and α1d‐adrenoceptors was studied using reverse transcription‐polymerase chain reaction (RT–PCR). RT–PCR demonstrated the strongest expression of the α1a‐adrenoceptor, weak expression of the α1b‐ adrenoceptor and undetectable expression of the α1d‐adrenoceptor.
The present study suggests that α1A‐adrenoceptor is a major subtype detectable in binding and RT–PCR studies in rabbit iris, but that the adrenergic contractions of iris dilator muscle are mediated via activation of α1‐adrenoceptor subtype having low affinity for prazosin and WB4101.
Subtypes of α1‐adrenoceptor in rabbit iris have been examined in functional, binding and molecular biological experiments.
In functional studies, exogenous and endogenous noradrenaline produced contractions of the iris dilator muscle. The contractile responses to noradrenaline were competitively antagonized by a range of α1‐adrenoceptor antagonists (pA2 values): prazosin (8.1), WB4101 (8.2), BMY7378 (5.9), YM617 (9.5), JTH‐601 (8.8), HV723 (7.8) and KMD‐3213 (9.8). The same order of inhibitory potency was seen in the adrenergic responses to electrical stimulation. This affinity profile corresponds well to that of the putative α1L‐adrenoceptor, which has been proposed in lower urinary tract tissues.
In binding studies on rabbit iris membrane however, prazosin, KMD‐3213 and WB4101 displayed high affinity (pKd or pKi: 9.6, 10.3, 9.6, respectively), and BMY7378 displayed low affinity (pKi: 6.9). These results show that the binding sites typically correspond to α1A‐adrenoceptor subtype in character, and we could not detect the significant amount of α1L‐adrenoceptor subtype.
The expression of the three distinct mRNAs that encode proteins of α1a‐, α1b‐ and α1d‐adrenoceptors was studied using reverse transcription‐polymerase chain reaction (RT–PCR). RT–PCR demonstrated the strongest expression of the α1a‐adrenoceptor, weak expression of the α1b‐ adrenoceptor and undetectable expression of the α1d‐adrenoceptor.
The present study suggests that α1A‐adrenoceptor is a major subtype detectable in binding and RT–PCR studies in rabbit iris, but that the adrenergic contractions of iris dilator muscle are mediated via activation of α1‐adrenoceptor subtype having low affinity for prazosin and WB4101.
British Journal of Pharmacology (1999) 127, 1367–1374; doi:10.1038/sj.bjp.0702675
DOI: 10.1038/sj.bjp.0702675
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