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Imidazoline receptors in relaxation of acetylcholine-constricted isolated rat jejunum.

Since 20 years the concept of specific imidazoline receptors has remained controversial. The problem with imidazoline receptors is mostly due to their functional similarity to alpha-adrenoceptors. In this work, a pharmacodynamic model of isolated rat jejunum longitudinal muscle strips constricted with acetylcholine (Ach) was applied to separate functional properties of the two types of receptors. Relaxation of the preparation was measured as a function of concentration of 2-(benzofuranyl)-2-imidazoline (2-BFI), a specific imidazoline I2 receptor ligand, cirazoline, a potent I2 receptor ligand and alpha1-adrenoceptor agonist, phenylephrine, an agonist of alpha1-adrenoceptor, moxonidine, a ligand of I1 receptor, efaroxan, a ligand of I3 receptor and 5-bromo-6-(imidazoline-2-yl-amino)quinoxaline (UK14304), an agonist of alpha2-adrenoceptor. Next, the effects of a series of imidazoline-and/or alpha-adrenoceptor-binding drugs (prazosin, yohimbine, RS79948, RX821002, idazoxan and efaroxan) on the relaxation of the Ach-constricted rat jejunum strips, induced by 2-BFI, cirazoline or phenylephrine, were studied. The obtained results demonstrate the involvement of the postsynaptic imidazoline receptors in rat jejunum motility. These receptors are of I2 subtype and are linked to alpha-adrenoceptors of the predominantly alpha1 subtype. The alpha1 receptors dominate functionally over the I2 in the isolated rat jejnum. The proposed model might be useful in search for more specific new drugs.