TY - JOUR
T1 - Human tissue adrenergic receptors are not predictive of responses to epinephrine in vivo
AU - Liggett, S. B.
AU - Shah, S. D.
AU - Cryer, P. E.
PY - 1989
Y1 - 1989
N2 - 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; β2), platelets (α2), skeletal muscle membranes (β2), and fat cells (B1 and α2) and compared with the responses to stepped, intravenous epinephrine infusions in vivo. MNL β2-adrenergic receptor densities (but not antagonist affinities) were correlated (r = 0.627; P < 0.01) with skeletal muscle β2-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 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.
AB - 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; β2), platelets (α2), skeletal muscle membranes (β2), and fat cells (B1 and α2) and compared with the responses to stepped, intravenous epinephrine infusions in vivo. MNL β2-adrenergic receptor densities (but not antagonist affinities) were correlated (r = 0.627; P < 0.01) with skeletal muscle β2-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 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.
UR - http://www.scopus.com/inward/record.url?scp=0024524990&partnerID=8YFLogxK
M3 - Article
C2 - 2541622
AN - SCOPUS:0024524990
VL - 256
SP - 19/5
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 5
ER -