The effect of endomorphins on the release of 3H-norepinephrine from rat nucleus tractus solitarii slices.
We used two, 3-min field stimulation cycles 30 min apart (S1, S2) in 3H-norepinephrine-loaded, superfused rat nucleus tractus solitarii-dorsal motor vagal nucleus (NTS-DVN) slices. The stimulation-induced release was expressed as the area above the baseline. Drugs were introduced 12 min before S2 and drug actions were characterized in terms of alterations of S2/S1 ratios. The S2/S1 ratio was 1.047 (0.946-1.159, n = 4, geometric mean and 95% confidence interval) in controls and 0.336 (0.230-0.490, n = 3), 0.726 (0.590-0.892, n = 4), 0.613 (0.594-0.683, n = 4) and 0.665 (0.500-0.886, n = 4) in the presence of 10(-6) M clonidine, D-Ala(2),MePhe(4),Gly(5)-ol-enkephalin (DAMGO), endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2), EM-1) and -2 (Tyr-Pro-Phe-Phe-NH(2), EM-2) [the latter two in the presence of 10(-4) M diprotin A, an inhibitor of dipeptidyl-aminopeptidase IV (DAP-IV) enzyme]. The effect of DAMGO at 10(-5) M was significantly higher than at 10(-6) M, whereas the effect of endomorphins did not differ at the two concentration levels. Diprotin A potentiated only very modestly the action of endomorphins. These data (a) confirm the presence of functional mu-opioid receptors in the vagal complex, (b) render it likely that the enzymic degradation of endomorphins is not a highly effective process in brain slices and (c) may suggest that the apparent ceiling in the effect of endomorphins might be related to their partial agonist property.
Al-Khrasani
Mahmoud
M
Faculty of Medicine, Department of Pharmacology and Pharmacotherapy, Semmelweis University, POB 370, H-1445, Budapest, Hungary. mahmoud@pharma.sote.hu
Elor
Guy
G
Yusuf Abbas
Mamode
M
Rónai
András Z
AZ
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism*; D014316:Tritium; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C105294:endomorphin 2; D003000:Clonidine; D009638:Norepinephrine