title: Human tissue adrenergic receptors are not predictive of responses to epinephrine in vivo.
abstract: To test the hypotheses that adrenergic receptor and adenylate cyclase characteristics of easily accessible circulating cells reflect those of relatively inaccessible extravascular catecholamine target tissues in a subtype-specific fashion and that these characteristics predict responses to catecholamines in vivo, we studied 22 normal humans. Adrenergic receptors and their linked adenylate cyclase systems were measured in mononuclear leukocytes (MNL; beta 2), platelets (alpha 2), skeletal muscle membranes (beta 2), and fat cells (B1 and alpha 2) and compared with the responses to stepped, intravenous epinephrine infusions in vivo. MNL beta 2-adrenergic receptor densities (but not antagonist affinities) were correlated (r = 0.627; P less than 0.01) with skeletal muscle beta 2-adrenergic densities. However, other adrenergic receptor characteristics and basal and maximally stimulated adenosine 3',5'-cyclic monophosphate (cAMP) contents of MNL and all adrenergic receptor characteristics and cAMP contents of platelets were unrelated to the corresponding measurements in skeletal muscle and fat. Furthermore, there were no consistent relationships between tissue adrenergic receptor-adenylate cyclase characteristics and the chronotropic, diastolic depressor, lipolytic, ketogenic, glycemic, or glycogenolytic-glycolytic responses to epinephrine in vivo. Thus the data support the hypothesis that adrenergic receptor densities on circulating cells reflect those of extravascular target tissues in a subtype-specific fashion. On the other hand, the data do not support the hypothesis that physiological interindividual variation of adrenergic receptor characteristics is of sufficient magnitude to alter sensitivity to epinephrine in vivo.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: S B
authors.initials: SB
authors.lastname: Liggett
authors.forename: S D
authors.initials: SD
authors.lastname: Shah
authors.forename: P E
authors.initials: PE
authors.lastname: Cryer
mesh_terms: D000262:Adenylyl Cyclases / Q000032:analysis; D000273:Adipose Tissue / Q000032:analysis; D000328:Adult; D001792:Blood Platelets / Q000032:analysis; D000242:Cyclic AMP / Q000032:analysis; D004837:Epinephrine / Q000097:blood / Q000502:physiology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000032:analysis; D008297:Male; D009132:Muscles / Q000032:analysis; D011941:Receptors, Adrenergic / Q000032:analysis*
chemical_list: D011941:Receptors, Adrenergic; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004837:Epinephrine