title: Alpha 1-adrenoceptor subtype in the rat prostate is preferentially the alpha 1A type.
abstract: alpha 1-Adrenoceptors in the rat prostate were characterized by a binding assay using the newly synthesized radioligand [3H]-YM617 (5-[2-[[2[ethoxyring(n)-3H](o-ethoxyphenoxy)ethyl]amino]prop yl]-2-methoxybenzenesulfonamide HCl) and an in vitro assay. Specific [3H]-YM617 binding in the rat prostate was saturable and of high affinity (KD = 61.5 +/- 5.9 pM) with 23.2 +/- 6.9 fmol/mg of protein as the maximal number of binding sites (Bmax). alpha-Adrenoceptor agonists and antagonists inhibited the binding of the radioligand with the following order of effectiveness: YM617 > prazosin = bunazosin > WB4101 > 5-methylurapidil = phenoxybenzamine > phentolamine > S(+)-isomer of YM617 > yohimbine > norepinephrine > phenylephrine > methoxamine. alpha 1-Adrenoceptors in the rat prostate preferred the R(-)-isomer of YM617 to the S(+)-isomer. Preincubation with chlorethylclonidine (CEC; 10(-5) M, 10 min) just slightly changed the Bmax value for [3H]-YM617 without changing the KD value in the prostate; however, CEC reduced the Bmax in the aorta. In the isolated tissue, pretreatment with CEC (10(-5) M, 10 and 30 min) time-dependently shifted to the right the dose-response curve for phenylephrine and decreased the maximal contraction of aortas induced by phenylephrine, but did not shift or decrease those of prostates. The present results indicate that the alpha 1-adrenoceptors in the rat prostate are mainly CEC-insensitive (alpha 1A), whereas those in the aorta are CEC-sensitive (alpha 1B).
authors.affiliation: Drug Serendipity Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yazawa
authors.forename: K
authors.initials: K
authors.lastname: Honda
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001665:Binding Sites; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013449:Sulfonamides / Q000378:metabolism*; D000077409:Tamsulosin
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000477:Alkylating Agents; D011942:Receptors, Adrenergic, alpha; D013449:Sulfonamides; C051731:chlorethylclonidine; D000077409:Tamsulosin; D003000:Clonidine