G-proteins in alpha 1-adrenoceptor mediated prostatic smooth muscle contraction.
The role of signal transducing guanine-nucleotide binding proteins (G-proteins) in alpha 1-receptor mediated smooth muscle contractions was investigated in human hyperplastic prostatic tissue. The selective alpha 1-receptor agonist phenylephrine (PE) evoked dose dependent contractions antagonized by the alpha 1-receptor blockers prazosin (EC50 10 nM) and YM617 (EC50 3 nM). Application of nifedipine (1-10,000 nM), a blocker of voltage-dependent L-type Ca(2+)-channels (VDCC), inhibited the PE evoked contraction up to 65.4%. Pretreating the tissue strips with pertussis toxin (PTX, exotoxin from Bordetella pertussis; 5-25 micrograms/ml), inactivating a subpopulation of G-proteins, inhibited the PE induced contractions up to 73.9%. PTX pretreatment had no effect on contractions elicited by 125 mM K+. Application of nifedipine to PTX pretreated tissue led to an additional inhibition of 13.7%. Our findings demonstrate the involvement of PTX-sensitive G-proteins in the signal transduction pathway of alpha 1-receptor induced contractions of prostatic smooth muscle. The remaining contractility of PTX pretreated tissue suggests additional participation of PTX insensitive mechanisms in alpha 1-receptor mediated prostatic smooth muscle contractions.
Drescher
P
P
Urology Section, VA Hospital, Madison, WI.
Eckert
R E
RE
Madsen
P O
PO
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011467:Prostate / Q000503:physiopathology*; D011470:Prostatic Hyperplasia / Q000503:physiopathology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D010656:Phenylephrine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009543:Nifedipine; D011188:Potassium