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Role of imidazole receptors in the vasodepressor response to clonidine analogs in the rostral ventrolateral medulla.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 1990 Apr; Vol. 253 (1), pp. 408-18. - Publication Year :
- 1990
-
Abstract
- The rostral ventrolateral medulla is the primary site of action for clonidine, a centrally acting antihypertensive. In the rostral ventrolateral medulla, clonidine binds not only to alpha-2 adrenergic receptors but also to specific imidazole sites. In order to determine whether a putative imidazole receptor mediates the hypotensive action of clonidine, a series of compounds was tested 1) in vitro for binding affinity at imidazole and alpha-2 sites and 2) in vivo for ability to lower arterial pressure and heart rate when microinjected directly into the rostral ventrolateral medulla. Hypotensive potency was correlated with affinity at imidazole sites (r = 0.84), but not with alpha-2 affinity (r = -0.05). The bradycardia elicited by this series of compounds also correlated with affinity at imidazole receptors (r = 0.89), but not with alpha-2 affinity (r = 0.10). Furthermore, the imidazole idazoxan selectively reversed the fall in arterial pressure elicited by clonidine, whereas SKF-86466, an alpha-2 antagonist which is not an imidazole, failed to attenuate clonidine's action. An imidazole receptor in the rostral ventrolateral medulla appears to mediate the central hypotensive actions of clonidine and related centrally acting imidazoles and may participate in the regulation of arterial pressure and heart rate.
- Subjects :
- Animals
Benzazepines pharmacology
Clonidine analogs & derivatives
Clonidine metabolism
Dose-Response Relationship, Drug
Heart Rate drug effects
Male
Rats
Rats, Inbred Strains
Receptors, Adrenergic, alpha metabolism
Receptors, Drug drug effects
Blood Pressure drug effects
Clonidine pharmacology
Imidazoles pharmacology
Medulla Oblongata drug effects
Receptors, Drug physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 253
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 2158551