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IMIDAZOLINE BINDING SITES AND SIGNAL TRANSDUCTION PATHWAYS
Author(s) -
Musgrave IF,
Krautwurst D.,
Schultz G.
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb01156.x
Subject(s) - imidazoline receptor , idazoxan , chemistry , nicotinic agonist , clonidine , acetylcholine receptor , signal transduction , ion channel , ligand gated ion channel , pharmacology , endocrinology , medicine , receptor , biophysics , biochemistry , biology , antagonist , prazosin
SUMMARY 1. Discrete, non‐adrenergic binding sites for imidazolines have been characterized in the brain and periphery. The 1 1 clonidine‐preferring site is mainly distributed in the brain and brain stem, while the 12 idazoxan‐preferring site is more widely distributed. 2. The 1 1 site appears to be associated with modulation of blood pressure. Imidazolines act within the rostral ventrolat ral medulla to produce hypotension. The underlying signal transduction mechanism is poorly understood. 3. The imidazolines clonidine and cirazoline inhibited nicotine‐stimulated calcium entry into rat phaeochromocytoma (PC‐12) cells by a non‐adrenergic mechanism. This effect was not attributable to the stimulation of protein kinases. 4. Similarly, clonidine and cirazoline inhibited nicotinestimulated inward currents into PC‐12 cells. This inhibitory action was not altered by inhibitors of signal transducing G‐proteins. 5. Clonidine and cirazoline displaced the ion channel ligand [ 3 H]‐phencyclidine from nicotinic acetylcholine receptors, suggesting that these drugs act by direct blockade of the intrinsic ion channel of the nicotinic acetylcholine receptor. 6. This ion channel‐blocking activity represents a novel action of these imidazolines and may underlie some of the proposed physiological actions of 1 1 sites.