Presynaptic alpha-2C adrenoceptor-mediated control of noradrenaline release in humans: genotype- or age-dependent?
In vitro alpha-2CDel322-325 adrenoceptor (AR) polymorphism exhibits reduced functional responsiveness. We studied whether this is true also in vivo in humans. We assessed in nine young wild-type (WT) alpha-2C AR subjects (aged 23 years), 10 elder WT alpha-2C AR subjects (aged 63 years), and nine alpha-2CDel AR subjects (aged 28 years) clonidine (1 microg/kg intravenous (i.v.) bolus)-evoked plasma noradrenaline (pNA), heart rate (HR), and blood pressure (BP) changes. Clonidine-evoked pNA decreases were comparable in young WT alpha-2C and in alpha-2CDel AR subjects, but significantly lower (P=0.033) in elder subjects. Similarly, clonidine-evoked HR decreases were significantly larger in young WT alpha-2C and in alpha-2CDel AR subjects than in elder subjects, whereas clonidine-evoked BP decreases were larger in elder subjects. In conclusion, alpha-2CDel AR appears to play only a minor role in presynaptic regulation of NA release and/or to be not hypofunctional in vivo in humans, but functional responsiveness of presynaptic alpha-2 AR declines with ageing.
Bruck
H
H
Departments of Nephrology and Pathophysiology, University of Essen Medical School, Essen, Germany.
Schwerdtfeger
T
T
Toliat
M
M
Leineweber
K
K
Heusch
G
G
Philipp
T
T
Nürnberg
P
P
Brodde
O-E
OE
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000375:Aging / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood* / Q000378:metabolism; D011110:Polymorphism, Genetic; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D009638:Norepinephrine