Direct relationship between mononuclear leukocyte and lung beta-adrenergic receptors and apparent reciprocal regulation of extravascular, but not intravascular, alpha- and beta-adrenergic receptors by the sympathochromaffin system in humans.
To examine putative relationships between adrenergic receptors on accessible circulating cells and relatively inaccessible extravascular catecholamine target tissues, we measured mononuclear leukocyte (MNL) and lung beta-adrenergic receptors and platelet and lung alpha-adrenergic receptors in tissues obtained from 15 patients undergoing pulmonary resection. Plasma catecholamine concentrations were measured concurrently to explore potential regulatory relationships between the activity of the sympathochromaffin system and both intravascular and extravascular adrenergic receptors. MNL and lung membrane beta-adrenergic receptor densities were correlated highly (r = 0.845, P less than 0.001). Platelet alpha 2-adrenergic receptor and lung alpha 1-adrenergic receptor densities were not. Lung alpha 1-adrenergic receptor densities were positively related to plasma norepinephrine (r = 0.840, P less than 0.01) and epinephrine (r = 0.860, P less than 0.01) concentrations; in contrast, lung beta-adrenergic receptor densities were not positively related to plasma catecholamine concentrations (they tended to be inversely related to plasma norepinephrine and epinephrine [r = -0.698, P less than 0.05] levels). This apparent reciprocal regulation of alpha- and beta-adrenergic receptors by the sympathochromaffin system was only demonstrable with adrenergic receptor measurements in the extravascular catecholamine target tissue. Neither MNL beta-adrenergic receptor nor platelet alpha-adrenergic receptor densities were correlated with plasma catecholamine levels. Thus, although measurements of beta-adrenergic receptors on circulating mononuclear leukocytes can be used as indices of extravascular target tissue beta-adrenergic receptor densities (at least in lung and heart), it would appear that extravascular tissues should be used to study adrenergic receptor regulation by endogenous catecholamines in humans. These data provide further support for the concept of up regulation, as well as down regulation, of some adrenergic receptor populations during short-term activation of the sympathochromaffin system in humans.
Liggett
S B
SB
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Marker
J C
JC
Shah
S D
SD
Roper
C L
CL
Cryer
P E
PE
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism / Q000502:physiology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011224:Prazosin; D011942:Receptors, Adrenergic, alpha / Q000032:analysis* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000502:physiology
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine