Enhancement of alpha-adrenoceptor-mediated responses in prostate of testosterone-treated rat.
The present study was undertaken to investigate the effect of testosterone on the alpha-adrenoceptor-mediated contractile responses in ventral lobe of rat prostate. Contractile responses to various alpha-adrenoceptor agonists (phenylephrine, A61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulphonamide), clonidine, guanfacine, ST587 ((2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[2-(2,6-dimethoxy-phenoxy)-ethyl]-amine) and xylazine) were tested in prostate strips obtained from control and testosterone (3 mg/kg, s.c. 5 days a week for 15 days-10 doses total)-treated rats. Dose-response curves for alpha-adrenoceptor agonists in testosterone-treated animals showed a leftward shift, indicating increased sensitivity of tissue to alpha-adrenoceptor agonists. To find the mechanism of increased sensitivity, K(A) value and receptor reserve of phenylephrine were estimated. Neither the K(A) value nor the receptor reserve of phenylephrine was altered in testosterone-treated rats. The concentration-occupancy curve for A61603 was shifted leftward and the K(A) value for A61603 decreased about four-fold. The K(B) value of 2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane (WB4101) was not altered, however, the K(B) value for prazosin was decreased approximately 5.5-fold. These findings indicate that the testosterone-mediated increase in sensitivity of prostate to alpha-adrenoceptor agonists is due to alterations in the alpha(1)-adrenoceptor pool.
Thiyagarajan
Meenakshisundaram
M
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Phase-10, SAS Nagar, Sector-67, Mohali, Punjab-160 062, India.
Kaul
Chaman Lal
CL
Ramarao
Poduri
P
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
C094643:A 61603; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D013764:Tetrahydronaphthalenes; D010656:Phenylephrine; D013739:Testosterone