Pharmacologic characterization of cirazoline-activated inositol phospholipid hydrolysis in rat brain cortical slices.
Interaction of cirazoline, an imidazoline derivative, with alpha 1-adrenoceptor coupled inositol phospholipid hydrolysis was characterized in rat brain cortical slices. Norepinephrine, a full alpha 1-agonist, and phenylephrine, a partial alpha 1-agonist, on inositol phospholipid hydrolysis were included for comparison. Norepinephrine produced a fourfold stimulation of inositol phospholipid hydrolysis, whereas cirazoline and phenylephrine caused only submaximal responses (40-60%) when compared with norepinephrine. The stimulation of inositol phospholipid hydrolysis by cirazoline was completely blocked by the alpha 1-adrenoceptor antagonist prazosin, but not by selective alpha 2- or beta-adrenoceptor antagonists. Furthermore, the norepinephrine dose-response curve was shifted to the right in the presence of cirazoline, without affecting the maximal response. These results suggest that cirazoline behaves as a partial agonist at brain alpha 1-adrenoceptors linked to inositol phospholipid hydrolysis.
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Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, Toronto, Ont., Canada.
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D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D006868:Hydrolysis; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism
D007093:Imidazoles; D010716:Phosphatidylinositols; D011941:Receptors, Adrenergic; D010656:Phenylephrine; C014282:cirazoline; D009638:Norepinephrine