Terbutaline-induced desensitization of polymorphonuclear leukocyte beta 2-adrenergic receptors in young and elderly subjects.
Potential age-related differences in cardiovascular responsiveness and receptor regulation induced by short-term administration of a selective beta 2-adrenergic receptor agonist were investigated. Young (age range, 23 to 31 years) and elderly (age range, 64 to 73 years) healthy subjects were treated with terbutaline (5 mg, three times daily) for 5 days. Similar plasma terbutaline concentrations were achieved in the two age groups. The elderly group had higher baseline plasma norepinephrine concentrations and mean arterial pressures, neither of which were altered by terbutaline administration. During terbutaline treatment, heart rate increased in both age groups while subjects were supine but consistently increased only in the young group while subjects were standing. In both age groups, the density of beta 2-adrenergic receptors on polymorphonuclear leukocyte membranes was reduced by 50% during terbutaline administration and returned to baseline values at similar rates after drug administration was stopped. Isoproterenol-stimulated cyclic adenosine monophosphate accumulation in polymorphonuclear leukocytes from elderly subjects was regulated similarly. These findings suggest that the ability of terbutaline to increase standing heart rate is selectively impaired in the elderly, whereas the ability of polymorphonuclear leukocyte beta 2-adrenergic receptors to down-regulate and to return to baseline values is not.
Zahniser
N R
NR
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Wiser
A
A
Cass
W A
WA
Curella
P
P
Gerber
J G
JG
Nies
A S
AS
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013726:Terbutaline / Q000097:blood / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D013726:Terbutaline; D009638:Norepinephrine