Mu and kappa opioid receptor modulation of 5-HT3 and NK-3 receptor-evoked release of acetylcholine from the guinea-pig ileum myenteric plexus
| Autor: | Alyson J. Fox, Ian K.M. Morton |
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| Rok vydání: | 1991 |
| Předmět: |
Agonist
Male medicine.medical_specialty Serotonin Pyrrolidines medicine.drug_class Guinea Pigs Receptors Opioid mu Myenteric Plexus (+)-Naloxone Substance P Tritium κ-opioid receptor Choline chemistry.chemical_compound Ileum Internal medicine medicine Animals Receptor Myenteric plexus Receptors Tachykinin Pharmacology Analgesics Chemistry Receptors Opioid kappa 3 4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide (trans)-Isomer Muscle Smooth General Medicine Enkephalins Enkephalin Ala(2)-MePhe(4)-Gly(5) Acetylcholine Peptide Fragments Receptors Neurotransmitter DAMGO Endocrinology Opioid Receptors Serotonin Receptors Opioid Enkephalin D-Penicillamine (2 5) medicine.drug Muscle Contraction |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 344(1) |
| ISSN: | 0028-1298 |
| Popis: | 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 (μ)-opioid receptor agonist (d-Ala2,NMe-Phe4,Gly-ol]-enkephalin) (DAMGO; 1 nM–100 nM) and the selective kappa (κ)-opioid receptor agonist U50488 (10 nM -1 μM) 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 (σ)-opioid receptor agonist [d-Pen2,5]-enkephalin (DPDPE) inhibited contractile responses only at the highest concentration used (1 μM). 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 μM) inhibited the increases in release of [3H]-ACh evoked by 5-HT (10 μM) and by senktide (10 nM) in a concentration-dependant 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 μM). The inhibitory effects of DAMGO, U50488 and DPDPE on contractions and [3H]-ACh release evoked by 5-HT and senktide were completely reversed by naloxone (10 μM). These results show that ACh release in the guinea-pig ileum evoked by 5-HT and senktide can be modulated to a similar extent by the opioid agonists DAMGO and U50488, but not by DPDPE. This suggests that the pathways of excitation for 5-HT3 and NK-3 receptors converge at some level susceptible to opioid inhibition, which may be mediated by μ- and κ-, but not σ-, opioid receptors. |
| Databáze: | OpenAIRE |
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