Effects of avermectin B1a and picrotoxin on striatal release of dopamine with reference to replacement of extracellular chloride with nitrate.
The present study was an attempt to elucidate the effects of avermectin B1a (AVM) and picrotoxin, an anion channel opener and blocker, respectively, on the release of endogenous dopamine from the slices of caudate nucleus of the rat, using a superfusion method in order to determine the interaction between these agents with the gamma-aminobutyric acid (GABA) receptor-anion channel complex. Avermectin (1.14-11.4 microM) reduced the Ca2+-dependent release of dopamine stimulated by 40 mM KCl without affecting the basal release of dopamine. In contrast, picrotoxin in doses larger than 20 microM facilitated the K+-stimulated release of dopamine. The inhibitory effect of avermectin was completely antagonized by 10 microM picrotoxin and 0.1 mM bicuculline; these doses of both agents did not change the K+-stimulated release of dopamine. Replacement of chloride (Cl-) in the superfusion medium with nitrate (NO3-) markedly facilitated the K+-stimulated release of dopamine and the increase was antagonized by verapamil (10 microM) and tetrodotoxin (1 microM). In the nitrate medium, avermectin reduced the K+-stimulated release of dopamine and the inhibitory effect was antagonized by bicuculline. However, picrotoxin up to 100 microM did not affect the K+-stimulated release of dopamine either in the presence or absence of bicuculline. These results suggest that the dopaminergic nerve terminals in the caudate nucleus receive inhibitory regulation through the facilitation of anion channels. This regulation is apparently altered depending on the main anion in the extracellular fluid.
D000596:Amino Acids / Q000494:pharmacology; D021542:Amino Acids, Neutral; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D007559:Ivermectin / Q000031:analogs & derivatives*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009566:Nitrates / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000596:Amino Acids; D021542:Amino Acids, Neutral; D001640:Bicuculline; D002712:Chlorides; D004298:Dopamine; D007559:Ivermectin; D007783:Lactones; D009566:Nitrates; D010852:Picrotoxin; D013779:Tetrodotoxin; D014700:Verapamil; D005680:gamma-Aminobutyric Acid; C022120:avermectin B(1)a; C013809:5-aminovaleric acid