In vivo mechanisms underlying dopamine release from rat nigrostriatal terminals: II. Studies using potassium and tyramine.
The brain microdialysis technique has been used to examine the in vivo effects of potassium and tyramine on dopamine (DA) release and metabolism in the striatum of halothane-anaesthetised rats. Increasing the concentration of potassium perfusing the dialysis probe (30-120 mM) induced a dose-related efflux of DA. A dose-related release of DA was also observed following addition of tyramine (1-100 microM) to the perfusing buffer. High concentrations of potassium were found to reduce the dialysate content of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid. No such effect was observed even when using the highest concentration of tyramine tested. Potassium-evoked DA release was facilitated by pretreatment with the DA uptake inhibitor nomifensine, was inhibited by depletion of extracellular calcium, and was not significantly affected by tetrodotoxin (TTX). The effect of tyramine on DA efflux was inhibited by nomifensine and was insensitive to both TTX and calcium depletion. These data suggest that potassium and tyramine induce release of DA via different mechanisms. Potassium-induced DA release involves a carrier-independent process and may utilise an exocytotic release mechanism. On the other hand, tyramine-induced DA release would appear to involve a carrier-dependent process. Depletion of vesicular stores of DA by pretreatment with reserpine did not significantly affect potassium-induced DA release, whereas a marked inhibition of the effects of tyramine was noted. However, in reserpinised animals the potassium-induced release of DA was inhibited by nomifensine, a result suggesting that a carrier-dependent release mechanism operates in the absence of vesicular DA.(ABSTRACT TRUNCATED AT 250 WORDS)
Fairbrother
I S
IS
University Department of Pharmacology, Edinburgh Medical School, Scotland, U.K.
Arbuthnott
G W
GW
Kelly
J S
JS
Butcher
S P
SP
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000172:deficiency; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009411:Nerve Endings / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013378:Substantia Nigra / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology*; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D009627:Nomifensine; D013779:Tetrodotoxin; D019805:alpha-Methyltyrosine; D012110:Reserpine; D011188:Potassium; D002118:Calcium; D004298:Dopamine; D014439:Tyramine