Pharmacological characterization of the imidazoline receptor which mediates inhibition of noradrenaline release in the rabbit pulmonary artery.

Imidazoline receptors involved in modulation of noradrenaline release were characterized in the rabbit pulmonary artery preincubated with [3H]noradrenaline and superfused with physiological salt solution containing cocaine, corticosterone and propranolol. Tritium overflow was evoked by transmural electrical stimulation. The alpha 2-adrenoceptor blocking imidazolines tolazoline, BDF 6100 [2-(2-imidazoline-2-ylamino)-isoindoline] and BDF 7572 (4,7-dichloro-derivative of BDF 6100) increased the electrically evoked 3H overflow; the concentration-response curves were bell-shaped. In contrast, two other imidazolines, i.e. moxonidine and clonidine, two guanidine derivatives structurally related to BDF 6100, i.e. aganodine and BDF 7579 [4-chloro(2-isoindolinyl)-guanidine], as well as the catecholamine noradrenaline concentration-dependently inhibited the evoked 3H overflow. The concentration-response curves for moxonidine, clonidine, aganodine, BDF 7579 and noradrenaline were shifted to the right by rauwolscine. The apparent pA2 value of rauwolscine against moxonidine was 8.22, whereas those against clonidine, aganodine, BDF 7579 and noradrenaline were in the range of 6.37-6.77 and, hence, considerably lower than reported for alpha 2-adrenoceptors. In the presence of rauwolscine an inhibitory effect was also observed with the alpha 2-adrenoceptor blocking imidazolines tolazoline, BDF 6100, BDF 7572, and the imidazoline ST 587 [2-(2-chloro-5-trifluoromethylphenylimino)-imidazoline]; the rank order of potency of all guanidines and imidazolines investigated was: aganodine greater than BDF 7579 greater than BDF 7572 greater than BDF 6100 greater than clonidine greater than ST 587 greater than moxonidine greater than tolazoline.(ABSTRACT TRUNCATED AT 250 WORDS)