Characterization of a1-adrenoceptor subtypes and pharmacological actions of their antagonists in human prostate

• Main Authors: Guh Jih-Hwa, 顧記華
• Other Authors: Teng Che-Ming、Ko Feng-Nien
• Format: Others
• Language: zh-TW
• Published: 1996
• Online Access: http://ndltd.ncl.edu.tw/handle/66140564711167482123

博士 === 國立臺灣大學 === 藥理學研究所 === 84 === In human prostate, both nifedipine and CEC produced significant inhibition of NA-induced contractions. These results indicated that NA-induced contractions in human prostate are mediated by both α1A- and α 1B- adrenoceptorsubtypes. In contrast, the putative α 1a- adrenoceptors in human prostate may be functionally confined to the synaptic region. Ouabain (1uM) did not induce contractile response per se but progressively increased the resting tone in human prostate. Form our experimental results it is suggested that the increased tone of human prostate following repeated excitation in the presence of ouabain is due to increased Ca2+entry and reduced efflux of Ca2+as a consequence of Na+pump inhibition by ouabain. In addition , Ouabain itself concentration-dependently induced agradual contraction, which occurred after a delay of 10-25 min. This effect is due mainly to an increase in noradrenaline release via an effect on the Na+-dependent Ca2+ influx system. The selectivity of (-)-discretamine for α1-adrenoceptor subtypes was evaluated by use of functional and binding studies in rat vas deferens, spleen and aorta, and in cultured DDT1MF-2and A10 cells. The selectivity of (-)-discretamine among various α 1-adrenoceptor subtypes is α1A : α1B : α1D=0.04 : 0.07 : 1.0. N-methy-actinodaphnine is more selective for the α1b-than for the α1a-drenoceptor subtype. The effects of N-allylsecoboldine,(-)-discretamine, (± )-govadine, (±)-THP and N-methyl-actinodaphnine on human prostates were investigated. Amongtheng N-allylsecoboldine exhibits greater potency against contraction to electrical field stimulation than that to PE, while N-methyl- actinodaphnine has greater potency against PE-induced contraction than that to electrical field stumulation in human prostate.