Opioid peptide inhibition of endogenous norepinephrine release from the A2 noradrenergic cell group in vitro.
We investigated the potential influence of opioid and melanotropic peptides on endogenous norepinephrine (NE) release from the A2 noradrenergic cell group of rats using a static, fixed-volume incubation procedure. Norepinephrine release from slices of caudal dorsomedial medulla (CDMM) was evoked by high potassium concentrations (20 and 60 mM) in a Ca(2+)-dependent and dose-related manner. Treatment with the potent melanotropin agonist [Nle4,D-Phe7] alpha-MSH(NDP-MSH) had no effect on K(+)-induced NE release. In contrast, human beta-endorphin1-31 significantly reduced K(+)-stimulated NE release, but not in the presence of naloxone. The highly-selective mu-opioid agonist [D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) also significantly reduced evoked NE release. The inhibitory effect of DAMGO was completely blocked by naloxone. Naloxone alone did not alter evoked NE release. The inhibitory effect of DAMGO was not enhanced by reducing the stimulatory concentration of K+. None of the peptides tested influenced basal NE release. These data indicate that melanotropin receptors do not regulate NE release in CDMM. In contrast, the opioid peptides DAMGO and beta-endorphin inhibit K(+)-stimulated release of endogenous NE. These data suggest a role for mu-opioid receptors in controlling NE release from A2 noradrenergic neurons.
Carr
J A
JA
Department of Biological Sciences, Texas Tech University, Lubbock 79409-3131, USA.
Gregg
K J
KJ
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology*; D009074:Melanocyte-Stimulating Hormones / Q000819:agonists; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018847:Opioid Peptides / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology
D004745:Enkephalins; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D000521:alpha-MSH; D001615:beta-Endorphin; C027756:MSH, 4-Nle-7-Phe-alpha-; D009074:Melanocyte-Stimulating Hormones; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine