G-PROTEINS IN ALPHA-1-ADRENOCEPTOR MEDIATED PROSTATIC SMOOTH-MUSCLE CONTRACTION

The role of signal transducing guanine-nucleotide binding proteins (G- proteins) in alpha1-receptor mediated smooth muscle contractions was i nvestigated in human hyperplastic prostatic tissue. The selective alph a1-receptor agonist phenylephrine (PE) evoked dose dependent contracti ons antagonized by the alpha1-receptor blockers prazosin (EC50 10nM) a nd YM617 (EC50 3 nM). Application of nifedipine (1-10,000 nM), a block er of voltage-dependent L-type Ca2+-channels (VDCC), inhibited the PE evoked contraction up to 65.4%. Pretreating the tissue strips with per tussis toxin (PTX, exotoxin from Bordetella pertussis; 5-25 mug/ml), i nactivating a subpopulation of G-proteins, inhibited the PE induced co ntractions up to 73.9%. PTX pretreatment had no effect on contractions elicited by 125 mM K+. Application of nifedipine to PTX pretreated ti ssue led to an additional inhibition of 13.7%. Our findings demonstrat e the involvement of PTX-sensitive G-proteins in the signal transducti on pathway of alpha1-receptor induced contractions of prostatic smooth muscle. The remaining contractility of PTX pretreated tissue suggests additional participation of PTX insensitive mechanisms in alpha1-rece ptor mediated prostatic smooth muscle contractions.