When suspended in vitro in isolated organ baths, segments of the rabbit ileum show a fairly strong and stable spontaneous activity, which derives from the continuous release of acetylcholine and the activation of muscarinic receptors, since the activity is completely eliminated by atropine. Dynorphin A pEC50: 8.6"0.07., neuropeptide Y and its congener human pancreatic polypeptide pEC50: 9.40"0.10., and nociceptin pEC50: 8.08"0.12. dose-dependently inhibit the spontaneous activity through the activation of receptors, which are specifically antagonised respectively by naloxone p A2: 7.17"0.12., 2-naphtalen-1-ylamino.-3-phenylpropionitrile JCF 104; p A2: 5.80"0.10., and wNphe1xnociceptin-1–13.NH2 p A2: 6.17"0.19.. This last compound, a selective nociceptin-receptor OP4. antagonist, inhibits the effect of nociceptin in a competitive manner, as demonstrated by Schild analysis. wNphe1xnociceptin-1–13.NH2 also antagonizes the effects of other OP4 receptor ligands such as the full agonist, nociceptin-1–13.-NH2, and the partial agonists, wPhe1cCH2–NH.Gly 2 xnociceptin-1–13.-NH2 intrinsic activity a E.s0.5. and Ac-RYYWK-NH2 a Es0.5., with p A2 values ranged from 5.8 to 6.2. These results indicate that the functional site mediating the inhibitory effect of nociceptin in the rabbit ileum, is pharmacologically identical to the OP4 sites of other species mouse, rat, guinea pig, man., since the potencies p A2 values. of the pure and competitive antagonist wNphe1xnociceptin-1–13.NH2 is very similar to the values obtained in the other species. Moreover, the rabbit ileum is one of the few isolated organs that allow classifying compounds, which interact with OP4 receptors as full agonists, partial agonists, or pure antagonists.
[Nphe(1)]nociceptin-(1-13)NH2 selectively antagonizes nociceptin effects in the rabbit isolated ileum
CALO', Girolamo;
2000
Abstract
When suspended in vitro in isolated organ baths, segments of the rabbit ileum show a fairly strong and stable spontaneous activity, which derives from the continuous release of acetylcholine and the activation of muscarinic receptors, since the activity is completely eliminated by atropine. Dynorphin A pEC50: 8.6"0.07., neuropeptide Y and its congener human pancreatic polypeptide pEC50: 9.40"0.10., and nociceptin pEC50: 8.08"0.12. dose-dependently inhibit the spontaneous activity through the activation of receptors, which are specifically antagonised respectively by naloxone p A2: 7.17"0.12., 2-naphtalen-1-ylamino.-3-phenylpropionitrile JCF 104; p A2: 5.80"0.10., and wNphe1xnociceptin-1–13.NH2 p A2: 6.17"0.19.. This last compound, a selective nociceptin-receptor OP4. antagonist, inhibits the effect of nociceptin in a competitive manner, as demonstrated by Schild analysis. wNphe1xnociceptin-1–13.NH2 also antagonizes the effects of other OP4 receptor ligands such as the full agonist, nociceptin-1–13.-NH2, and the partial agonists, wPhe1cCH2–NH.Gly 2 xnociceptin-1–13.-NH2 intrinsic activity a E.s0.5. and Ac-RYYWK-NH2 a Es0.5., with p A2 values ranged from 5.8 to 6.2. These results indicate that the functional site mediating the inhibitory effect of nociceptin in the rabbit ileum, is pharmacologically identical to the OP4 sites of other species mouse, rat, guinea pig, man., since the potencies p A2 values. of the pure and competitive antagonist wNphe1xnociceptin-1–13.NH2 is very similar to the values obtained in the other species. Moreover, the rabbit ileum is one of the few isolated organs that allow classifying compounds, which interact with OP4 receptors as full agonists, partial agonists, or pure antagonists.Pubblicazioni consigliate
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