Calcium-dependent contractile response of arterial smooth muscle to a jellyfish toxin (pCrTX: Carybdea rastonii).
The purpose of the present experiments was to investigate the pharmacological mechanisms of the vasoconstriction caused by the toxin (pCrTX) which had been partially purified from the tentacles of the jellyfish Carybdea rastonii ('Andonkurage'). pCrTX (0.1 to 10 micrograms ml-1) produced a tonic contraction of rabbit aortic strips, which was nearly abolished in Ca2+-free medium and was significantly reduced by verapamil or diltiazem. pCrTX stimulated 45Ca2+-influx and this effect was markedly attenuated by verapamil. pCrTX-induced vasoconstriction was significantly attenuated by phentolamine, 6-hydroxydopamine (6-OHDA) and in low Na+-medium, but not by bretylium, guanethidine, reserpinization or tetrodotoxin (TTX). pCrTX continuously and significantly increased the 3H-efflux from [3H]-noradrenaline preloaded aortic strips and this effect was completely inhibited by pretreatment with 6-OHDA and in Ca2+-free medium, but not by phentolamine, bretylium, guanethidine or TTX. A single exposure to pCrTX for 30 min greatly reduced the contractile responses to tyramine, nicotine and transmural electrical stimulation, but not those to noradrenaline or KC1. In addition, incorporation of [3H]-noradrenaline was reduced. Pretreatments with chlorphenylamine or indomethacin failed to modify the contractile response to pCrTX. These results suggest that the pCrTX-induced vasoconstriction is caused by a presynaptic action, releasing noradrenaline from the intramural adrenergic nerve terminals, and by a postsynaptic action, which consists at least in part of stimulation of the transmembrane calcium influx. Both pre- and postsynaptic actions depend on the external calcium concentration. The data further suggest that pCrTX damages the noradrenaline uptake and/or storage mechanisms without damaging postsynaptic contractile systems.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012110:Reserpine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D003064:Cnidarian Venoms; D006892:Hydroxydopamines; D011189:Potassium Chloride; D012110:Reserpine; D016627:Oxidopamine; D002118:Calcium; D009638:Norepinephrine