Multiple opiate receptors may be involved in suppressing gamma-aminobutyrate release in substantia nigra.
Slices of rat substantia nigra were preloaded with tritiated gamma-aminobutyrate (GABA) or dopamine (DA) and perfused with Krebs solution containing 5 microM aminooxyacetic acid or 10 microM nialamide to inhibit the catabolism of GABA and DA respectively. Repeated brief exposures to high potassium medium (+ 30 mM K+ for 1 min) evoked a consistent pattern of calcium-dependent 3H efflux against which the effects of opiates (10-400 microM) were assessed. Opiate agonists inhibited K+-induced 3H-GABA efflux in the following decreasing order of potency: bremazocine greater than D-Ala2-Met5-enkephalinamide (ENK) greater than SKF 10047 much greater than morphine, consistent with the participation of kappa, delta, sigma and to a lesser extent mu opiate receptors respectively. Naloxone (1 microM) partially antagonised the response to morphine and ENK, while ICI 154129 attenuated ENK only. Save for a GABA-releasing action of SKF 10047 at high doses, none of the compounds altered basal outflow of 3H-GABA. Naloxone, in the dose range 10-400 microM, also significantly inhibited depolarisation-induced release of 3H-GABA. In parallel experiments none of the compounds tested were found to influence 3H-DA release in concentrations up to 40 microM, but thereafter suppressed K+-induced 3H-DA outflow indiscriminately. The results are discussed with reference to the possible mechanism(s) via which injected and endogenous opiates may affect motor performance by attenuating GABA transmission in the nigra.
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009526:Nialamide / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D013378:Substantia Nigra / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001575:Benzomorphans; D011957:Receptors, Opioid; D000625:Aminooxyacetic Acid; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; C012134:SK&F 10047; C027248:bremazocine; D010620:Phenazocine; D009526:Nialamide; D004298:Dopamine