Mu and kappa opioid receptor modulation of 5-HT3 and NK-3 receptor-evoked release of acetylcholine from the guinea-pig ileum myenteric plexus.
The effects of three different opioid agonists on contractions and [3H]-acetylcholine (ACh) release evoked by 5-hydroxytryptamine3 (5-HT3) and neurokinin-3 (NK-3) receptor activation were examined in the guinea-pig ileum longitudinal muscle-myenteric plexus strip (LMMP) preparation. The selective mu (mu)-opioid receptor agonist (D-Ala2,NMe-Phe4,Gly-ol]-enkephalin (DAMGO; 1 nM-100 nM) and the selective kappa (kappa)-opioid receptor agonist U50488 (10 nM-1 microM) inhibited contractile responses to 5-HT and to the selective NK-3 receptor agonist senktide, producing a concentration-related progressive flattening of their concentration-response curves. IC50 estimates for DAMGO and U50488 were somewhat higher for inhibition of 5-HT-evoked as compared to senktide-evoked contractions, and overall lay in the range 6 nM-51 nM. The selective delta (delta)-opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE) inhibited contractile responses only at the highest concentration used (1 microM). 3H-overflow from LMMP preparations preincubated with [3H]-choline was measured as an indicator of [3H]-ACh release. DAMGO (1 nM-100 nM) and U50488 (10 nM-1 microM) inhibited the increases in release of [3H]-ACh evoked by 5-HT (10 microM) and by senktide (10 nM) in a concentration-dependent manner. IC50 estimates for DAMGO and U50488 were not significantly different for inhibition of 5-HT as compared to senktide-evoked increases in [3H]-ACh release and lay in the range 6 nM-23 nM. DPDPE again only inhibited these responses at the maximum concentration used (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Fox
A J
AJ
Divison of Biomedical Sciences, King's College London, UK.
Morton
I K
IK
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000109:Acetylcholine / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002794:Choline / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000648:ultrastructure; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology / Q000648:ultrastructure; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin / Q000502:physiology*; D018039:Receptors, Tachykinin; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014316:Tritium
D000700:Analgesics; D004745:Enkephalins; D010446:Peptide Fragments; D011759:Pyrrolidines; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D018039:Receptors, Tachykinin; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C054724:senktide; D012701:Serotonin; D013373:Substance P; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D002794:Choline; D000109:Acetylcholine