Effects of different agents on the contractile response elicited by extracellular calcium after depletion of internal calcium stores in rat isolated aorta.
Noradrenaline, 1 microM, induced a sustained contractile response in rat isolated aorta in the presence and in the absence of extracellular Ca2+. After depleting the noradrenaline-sensitive intracellular Ca2+ stores, an increase in the basal tone of the aorta was observed during the incubation period in the presence of Ca2+ and in the absence of the agonist. We have tested the possible pathways through which Ca2+ enters the cell to refill the previously depleted Ca2+ pools, a process that is accompanied by an increase in tension. The magnitude of this increase does not depend on the presence of Mg2+ in the extracellular medium nor on the temperature, suggesting that it is mediated by an event that does not depend on intracellular energy or Ca2+, Mg(2+)-ATPase. It is inhibited in a concentration-dependent manner by an unspecific relaxing compound, caffeine, and an organic Ca2+ entry blocker, verapamil, but not by an inorganic Ca2+ entry blocker, lanthanum. Caffeine (10 mM) and verapamil (10(-5) M) completely inhibited the increase in the resting tone, but only verapamil abolished the refilling of the noradrenaline-sensitive Ca2+ pools, indicating that the extracellular Ca2+ enters the cell through voltage-operated Ca2+ channels. Caffeine inhibited the increase in the resting tone without blocking the refilling process of the stores at 37 degrees C, but at 25 degrees C a partial inhibition of the repletion of internal Ca2+ pools was observed. These results confirm previous work that showed a temperature-dependent activity of caffeine.
Noguera
M A
MA
Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, Spain.
D'Ocon
M P
MP
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000172:deficiency* / Q000378:metabolism / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature; D014700:Verapamil / Q000494:pharmacology
D002110:Caffeine; D007811:Lanthanum; D014700:Verapamil; D008274:Magnesium; D002118:Calcium; D009638:Norepinephrine