Alpha(2A)-adrenergic versus imidazoline receptor controversy in rilmenidine's action: alpha(2A)-antagonism in humans versus alpha(2A)-agonism in rabbits.
At the alpha(2A)-autoreceptors on the sympathetic nerve terminals of the human atrial appendages and rabbit pulmonary artery, rilmenidine and oxymetazoline exhibit different properties (antagonism and agonism, respectively). These opposite pharmacodynamic properties of alpha(2)-adrenoceptor ligands seem to be due to substantial differences in the nucleotide and amino acid sequences between human and rabbit alpha(2A)-adrenoceptors. Hence, the rabbit alpha(2A)-adrenoceptor is not reliably predictive for the action of ligands at the human alpha(2A)-adrenoceptor.
Molderings
Gerhard J
GJ
University of Bonn, Institute of Pharmacology and Toxicology, Bonn, Germany. molderings@uni-bonn.de
Bonisch
Heinz
H
Bruss
Michael
M
Gothert
Manfred
M
D000316:Adrenergic alpha-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D054755:Imidazoline Receptors; D008969:Molecular Sequence Data; D010080:Oxazoles / Q000378:metabolism* / Q000494:pharmacology; D010109:Oxymetazoline / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D000077769:Rilmenidine; D016415:Sequence Alignment
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D054755:Imidazoline Receptors; D010080:Oxazoles; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D010109:Oxymetazoline; D000077769:Rilmenidine