Effect of pressure on the release of endogenous dopamine from rat striatum and the role of sodium-calcium exchange.
Exposure to environmental pressures in excess of 20 atm abs can precipitate a hyperexcitability state known as high pressure neurologic syndrome (HPNS). Little is known about the underlying neurochemical basis of this syndrome. An in vitro model of the synthesis and release of endogenous dopamine (DA) from rat striatal slices has been used to examine the mechanism underlying the effects of high pressures of He. He at 100 atm abs produced changes in DA release which were strikingly similar to those of the cardiac glycoside, ouabain. Neither pressure nor ouabain (1-10 microM) had any significant effects on the spontaneous (nonevoked) release of DA or its metabolite 3,4-dihydroxyphenylacetic acid, but both pressure and ouabain significantly enhanced the stimulated release of DA which was evoked by a 6-min exposure to 35 mM KCl (P less than 0.05 and P less than 0.001). In both cases, this effect was dependent on the presence of extracellular Ca2+. Augmentation of evoked DA release by both ouabain and He pressure was reversed (P less than 0.05) by 3,4-dichlorobenzamil, a selective antagonist of the membrane Na+/Ca2+ exchange mechanism. The results suggest that pressure exerts its effects on DA release by increasing intracellular-free Ca2+ exchange after pressure-inhibition of the activity of the membrane Na,K-ATPase.
Paul
M L
ML
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
Philp
R B
RB
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006371:Helium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006610:High Pressure Neurological Syndrome / Q000378:metabolism*; D008297:Male; D010042:Ouabain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015102:3,4-Dihydroxyphenylacetic Acid; C041470:3',4'-dichlorobenzamil; D006371:Helium; D010042:Ouabain; D000584:Amiloride; D011188:Potassium; D002118:Calcium; D004298:Dopamine