Endothelin-1-induced contractions of isolated pig detrusor and vesical arterial smooth muscle: calcium dependence and phosphoinositide hydrolysis.
1. In isolated pig detrusor and vesical arterial smooth muscle preparations, endothelin-1 (ET-1) caused concentration-dependent contractions. Nifedipine (10(-6) M) did not significantly affect the action of ET-1 in the vessels, but almost abolished its effect in the detrusor. Incubation for 30 min in Ca(2+)-free solution markedly reduced the ET-1-induced contractions in both detrusor and vesical arteries. 2. The protein kinase C inhibitor H-7 (3 x 10(-5) M), reduced the response to ET-1 in detrusor muscle as well as in vessels, and abolished the contractions evoked by ET-1 in Ca(2+)-free solution. 3. ET-1 caused an increase in the accumulation of inositol phosphates (IPs) in preparations prelabelled with myo-[3H]inositol. After exposure to ET-1 (10(-7) M) for 60 min, an approx. 4-fold increase in IPs levels were demonstrated, compared to untreated controls, in both detrusor and vessel preparations. Pretreatment with nifedipine (10(-6) M) did not reduce IPs formation. In contrast, no increase in IPs formation was demonstrated in Ca(2+)-free medium. 4. The increase in accumulation of IPs was slow in onset in both detrusor and vesical arteries, with no significant accumulation demonstrable during the first 30 min. Time-course studies of tension development for ET-1 revealed that maximum tension was reached before significant levels of IPs could be detected.
Persson
K
K
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Garcia-Pascual
A
A
Holmquist
F
F
Andersson
K E
KE
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006868:Hydrolysis; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D001743:Urinary Bladder / Q000098:blood supply
D016232:Endothelins; D007546:Isoquinolines; D010716:Phosphatidylinositols; D010879:Piperazines; D009532:Nickel; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D002118:Calcium