Effects of khellin on contractile responses and 45Ca2+ movements in rat isolated aorta.
The effects of khellin on contractile responses and 45Ca2+ flux have been studied in rat isolated aortae. Khellin (10(-5)-3.2 x 10(-4) M) produced a concentration-dependent inhibition of noradrenaline (10(-6) M) and high K+ (80 mM)-induced contractions. At 3.2 x 10(-4) M, khellin increased cAMP levels and reduced 45Ca2+ influx in resting tissues and in tissues stimulated by noradrenaline (10(-5) M) and high K+ without affecting basal 45Ca2+ efflux or noradrenaline induced 45Ca2+ efflux. It is concluded that in rat isolated aorta, khellin caused a non-specific inhibition of Ca2+ influx but may also exhibit intracellular actions, thus decreasing the availability of Ca2+ required for activation. One or more of these mechanisms may be related to an increase in intracellular cAMP levels.
Department of Pharmacology, Laboratory of Pharmacognosy and Pharmacodynamics, School of Pharmacy, Valencia, Spain.
A
A
Ubeda
T
T
Tejerina
J
J
Tamargo
A
A
Villar
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D007666:Khellin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D007666:Khellin; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine