Characterization of alpha 1-adrenoceptor subtypes in tension response of human prostate to electrical field stimulation.
1. The effects of various alpha 1-adrenoceptor antagonists and nifedipine on tension responses of human prostate to electrical field stimulation were evaluated in this study. 2. Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl-urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension responses to electrical field stimulation and completely abolished them in the maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast, chloroethylclonidine (CEC), in the maximal concentration of 100 microM, blocked these effects by only 50%. 3. The contractile responses of rat vas deferens and spleen to exogenously-applied alpha 1-adrenoceptor agonists were competitively inhibited by prazosin and 5-methyl-urapidil; in addition, the pA2 values were calculated and the relative potencies with reference to prazosin were obtained. The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to that in rat vas deferens (0.257), which contains primarily putative alpha 1A-adrenoceptors. However, it was much more than that in rat spleen (0.011), which contains primarily putative alpha 1B-adrenoceptors. 4. Nifedipine (10(-8) to 10(-6) M) inhibited concentration-dependently the contractile responses to electrical field stimulation in human prostate; in addition, the inhibition percentages were similar to those to exogenously-applied noradrenaline in rat vas deferens. In contrast, CEC (10 microM), which almost flattened the concentration-response curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the nerve-mediated contraction of human prostate. 5. The involvement of prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of human prostate was also examined. Clonidine (3 x 10-9 to 3 x 10- M) blocked concentration-dependently the contractile response to electrical field stimulation of human prostate and this inhibitory effect was reversed by yohimbine (10-7 M). Additionally, the inhibitory effect of CEC (3 x 10-6 to 3 x 10-4 M)to the nerve-mediated contraction was also partially reversed by yohimbine (10-7 M).6. It is suggested that the putative czA-adrenoceptors in human prostate may be functionally confined to the synaptic region whereas only minor populations of the putative alpha 1B- and/or alpha 1c-adrenoceptors exist in this region.
Guh
J H
JH
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Chueh
S C
SC
Ko
F N
FN
Teng
C M
CM
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism*; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D018674:Adrenergic Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; D015016:Yohimbine; C051731:chlorethylclonidine; D009543:Nifedipine; D003000:Clonidine; D011224:Prazosin