title: Presynaptic alpha-2C adrenoceptor-mediated control of noradrenaline release in humans: genotype- or age-dependent?
abstract: 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.
authors.affiliation: Departments of Nephrology and Pathophysiology, University of Essen Medical School, Essen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bruck
authors.forename: T
authors.initials: T
authors.lastname: Schwerdtfeger
authors.forename: M
authors.initials: M
authors.lastname: Toliat
authors.forename: K
authors.initials: K
authors.lastname: Leineweber
authors.forename: G
authors.initials: G
authors.lastname: Heusch
authors.forename: T
authors.initials: T
authors.lastname: Philipp
authors.forename: P
authors.initials: P
authors.lastname: Nürnberg
authors.forename: O-E
authors.initials: OE
authors.lastname: Brodde
mesh_terms: 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*
chemical_list: D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D009638:Norepinephrine