Characterization of alpha 1-adrenoceptor subtypes in prostate and prostatic urethra of rat, rabbit, dog and man.
The alpha 1-adrenoceptor subtypes present in the smooth muscle of urethra and prostate of different animal species, including man, were characterized by using receptor binding techniques. In prostatic urethra and prostate membranes, [3H]prazosin labelled a single population of alpha 1-adrenoceptors (Hill coefficient not different from unity) with a high affinity in the range 0.21-0.51 nM. The number of specific [3H]prazosin binding sites was partially affected by chloroethylclonidine only in human and rat prostate membranes, whereas this agent proved practically devoid of activity in rabbit and dog prostate membranes as well as in the prostatic urethra membranes of all the animal species examined. These findings indicate that in prostatic and urethral membranes the alpha 1-adrenoceptors mainly belong to the alpha 1A subtype. The binding results were confirmed by in vitro functional studies on noradrenaline-induced contractions of rabbit and dog urethral preparations. The agonist-induced contractions were practically unaffected by preincubation of both tissues with chloroethylclonidine, but were sensitive to nifedipine. We found, moreover, a good correlation between the potency of different selective and non-selective alpha 1-adrenoceptor antagonists (WB-4101, 5-methylurapidil, phentolamine, spiperone, prazosin and urapidil) tested against the noradrenaline-induced contractions of rabbit urethra and their affinity for the alpha 1A-adrenoceptor subtype, no correlation with the affinity for the alpha 1B subtype, and a lower correlation with the affinity for the alpha 1C-adrenoceptor subtype.
Testa
R
R
Research Laboratories, Recordati S.p.A., Milan, Italy.
Guarneri
L
L
Ibba
M
M
Strada
G
G
Poggesi
E
E
Taddei
C
C
Simonazzi
I
I
Leonardi
A
A
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism* / Q000502:physiology; D013045:Species Specificity; D014521:Urethra / Q000187:drug effects / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000477:Alkylating Agents; D018340:Receptors, Adrenergic, alpha-1; C051731:chlorethylclonidine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin