title: Interaction of clonidine and clonidine analogs with human platelet alpha 2-adrenergic receptors.
abstract: Several new clonidine analogs were synthesized and their ability to inhibit [3H]phentolamine binding to human platelet alpha 2-adrenergic receptors was tested. The order of potency and calculated dissociation constants for clonidine and its analogs were as follows: clonidine (0.020 +/- 0.005 microM) greater than p-aminoclonidine (0.100 +/- 0.010 microM) greater than hydroxy-phenacetyl-aminoclonidine (0.20 +/- 0.03 microM) greater than p-dansyl clonidine (1.00 +/- 0.20 microM) greater than t-boc-tyrosine clonidine (1.80 +/- 0.60 microM). Thus, p-amino substitution reduces alpha 2-adrenergic affinity in the platelet system. The effects of clonidine and its p-amino analogs on platelet adenylate cyclase were also evaluated. This enzyme is inhibited by epinephrine acting via alpha 2-adrenergic receptors. Both clonidine and p-aminoclonidine cause slight inhibition of basal adenylate cyclase and reverse the inhibition induced by epinephrine. These observations indicate that clonidine is a partial agonist for platelet alpha 2-adrenergic receptors.
mesh_terms: D000262:Adenylyl Cyclases / Q000097:blood; D000316:Adrenergic alpha-Agonists / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000097:blood*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010646:Phentolamine / Q000097:blood; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; C016986:apraclonidine; D000262:Adenylyl Cyclases; D003000:Clonidine; D004837:Epinephrine; D010646:Phentolamine