The mechanism of Ptychodiscus brevis toxin-induced rat vas deferens contraction.
Ptychodiscus brevis, which causes Florida red tide, produces Ptychodiscus brevis toxin (PBTX) known to contain neurotoxins and to induce rhinorrhea, tearing, and cough in normal humans and wheezing in asthmatic subjects. It was previously reported (J Allergy Clin Immunol 69:418, 1982; 73:824, 1984) that PBTX causes canine tracheal smooth muscle contraction via stimulation of sodium channels in the axons of parasympathetic postganglionic nerves and the release of acetylcholine from these nerve endings. This was postulated to be an asthma-triggering mechanism. In this article the toxins were evaluated to determine if they also stimulate sodium channels on adrenergic nerve endings and release norepinephrine. Rat vas deferens was selected as the experimental tissue. Both PBTX and norepinephrine contracted rat vas deferens. Prazosin 10(-6) mol/L blocked the response to PBTX (3 micrograms/ml) (88.3% to 27.3% contraction [n = 6; p less than 0.001]) and the response to norepinephrine (EC50 was shifted from 1.67 X 10(-6) mol/L to 1.25 X 10(-4) mol/L in the presence of prazosin 10(-6) mol/L [n = 6; p less than 0.001]). Phentolamine 10(-6) mol/L also blocked both PBTX and norepinephrine. Tetrodotoxin 10(-7) mol/L, a sodium channel blocker, completely blocked the response to PBTX but not to norepinephrine. The response to PBTX was significantly reduced from 1.53 gm of tension in controls to 0.29 gm of tension (n = 6; p = 0.002) in tissues obtained from rats pretreated with reserpine (2 mg/kg per day for 2 days, injected intraperitoneally). Verapamil 10(-5) mol/L blocked the PBTX response, and PBTX caused no contraction in calcium-free media.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004141:Dinoflagellida; D004305:Dose-Response Relationship, Drug; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens; D014700:Verapamil / Q000494:pharmacology
D008387:Marine Toxins; D009498:Neurotoxins; D011941:Receptors, Adrenergic; D013779:Tetrodotoxin; D012110:Reserpine; D014700:Verapamil; D009638:Norepinephrine