Stimulus-evoked release of tritiated monoamines from rat periaqueductal gray slices in vitro and its receptor-mediated modulation.
The periaqueductal gray is a brain region of considerable interest. It is innervated by monoamine-containing neurons as well as by a variety of peptidergic fiber systems, and it participates in the regulation of various functions. Virtually nothing is known about monoamine release in the periaqueductal gray and its receptor-mediated modulation. We therefore studied the release of radioactivity from periaqueductal gray slices preloaded with tritriated monoamines, using an in vitro superfusion method. The release of radioactivity from superfused periaqueductal gray slices after preloading of the tissue with [3H]noradrenaline increased upon electrical stimulation in a frequency-dependent manner. The stimulus-evoked release of radioactivity was Ca(2+)-dependent. Clonidine reduced and yohimbine enhanced the release. The inhibition curve for the effect of clonidine was shifted to the right in the presence of 10(-6) M yohimbine. While phenylephrine, isoprenaline, SK & F 38393, quinpirole, carbachol, [Arg8]vasopressin, alpha-MSH and ACTH-(1-24), at a concentration of 10(-6) M, did not influence the electrically evoked release of radioactivity, [Leu5]enkephalin reduced it. The selective mu-opioid receptor agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin and [D-Arg2,Lys4]-demorphin-(1----4)-amide reduced the release of radioactivity, whereas the selective delta opioid receptor agonist [D-Pen2,D-Pen5] enkephalin and the selective kappa opioid receptor agonist U-69593 had no effect. In the presence of naloxone, which by itself had no effect on the release of radioactivity, the effect of [D-Arg2,Lys4]dermorphin-(1-4)-amide was abolished. These results show that the release of noradrenaline from periaqueductal gray slices is via a Ca(2+)-dependent exocytotic process, and that it is modulated through alpha 2-adrenoceptors as well as via mu-opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Versteeg
D H
DH
Department of Pharmacology, Rudolf Magnus Institute, Medical Faculty, Utrecht University, The Netherlands.
Csikós
T
T
Spierenburg
H
H
D000818:Animals; D001337:Autonomic Agents / Q000494:pharmacology; D044482:Benzeneacetamides; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D012701:Serotonin / Q000378:metabolism*
D001337:Autonomic Agents; D044482:Benzeneacetamides; D009479:Neuropeptides; D011759:Pyrrolidines; D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D012701:Serotonin; C045444:U 69593; D004298:Dopamine; D009638:Norepinephrine