Nicardipine actions on smooth muscle cells and neuromuscular transmission in the guinea-pig basilar artery.
The effects of nicardipine on smooth muscle cells of the guinea-pig basilar artery were investigated by means of microelectrode and isometric tension recording methods. Nicardipine (1 X 10(-8) to 3 X 10(-6) M) did not modify the membrane potential and resistance of smooth muscle cells. The spike evoked by application of outward current pulse in the presence of tetraethylammonium (greater than 1 X 10(-3) M) was inhibited by 1 X 10(-9) M and was almost blocked by 3 X 10(-7) M nicardipine. Perivascular nerve stimulation evoked the excitatory junction potential which was slightly suppressed by 3 X 10(-6) M nicardipine. The contractions evoked by excess concentration of [K]0, NaCl-free solution or ATP was abolished and by 5-hydroxytryptamine was markedly inhibited in Ca-free ethylene glycol bis(beta-aminoethyl ether)N,N'-tetracetic acid-containing solution, but that induced by caffeine was only slightly inhibited. Nicardipine (greater than 3 X 10(-10) M) markedly inhibited the K-induced contraction noncompetitively as estimated from the Lineweaver-Burk's plot. The ATP-induced contractions were slightly inhibited by nicardipine (greater than 1 X 10(-8) M) to a lesser extent than the K-induced contraction. On the other hand, nicardipine (1 X 10(-6) M) had no effect on the NaCl-free-or 5-hydroxytryptamine-induced contraction. When nicardipine (1 X 10(-6) M) was applied during 2.5 mM Ca loading to muscle cells after depletion of the stored Ca, the subsequently generated caffeine-induced contraction was slightly inhibited due to inhibition of the passive Ca influx. These results indicate that nicardipine possesses a selective inhibitory action for the Ca channel, but the inhibition is limited to particular Ca influxes such as the voltage-dependent one, but not the receptor operated and NaCl-free-induced Ca influxes. This agent acts predominantly on the postjunctional muscle rather than the prejunctional nerve terminal.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000294:innervation / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology*; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
D011725:Pyridines; D000255:Adenosine Triphosphate; D009529:Nicardipine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium