Inhibitory effects of potassium channel blockers on carbachol-induced contraction in rat detrusor muscle.
We present accidental findings that potassium channel blockers, such as tetraethyl-ammonium (TEA) or 4-aminopyridine (4-AP), inhibit the sustained tonic contraction induced by carbachol in rat detrusor muscle strips. The relatively lower concentrations (<2 mM) of TEA and 4-AP inhibited phasic and tonic contractions induced by 5 micro M carbachol, whilst the relatively higher concentrations of TEA and 4-AP (>5 mM) potentiated phasic contractions. The potentiation of phasic contraction was not observed in nicardipine pretreated condition. In nicardipine pretreated condition, the concentration-response curves for the negative inotropic effect of potassium channel blockers were shifted to the right by the increasing concentration of carbachol from 0.5 microM to 5 microM. IC50 was changed significantly from 0.19 to 0.64 mM (TEA) and from 0.21 to 0.96 (4-AP). Such inhibitory effects were also observed in Ca2+ depleted condition, where 0.1 mM EGTA and 1 microM thapsigargin were added into Ca2+ free solution. In conclusion, inhibitory effects of potassium channel blockers on carbachol-induced contraction may be ascribed to the direct inhibition of receptor-agonist binding.
Oh
Seung-June
SJ
Department of Urology, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Ahn
Seung Cheol
SC
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009529:Nicardipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D001743:Urinary Bladder / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D019789:Tetraethylammonium; D002217:Carbachol; D015761:4-Aminopyridine; D009529:Nicardipine; D002118:Calcium