Presynaptic alpha-2C adrenoceptor-mediated control of noradrenaline release in humans: genotype- or age-dependent?

• Published in: Clinical pharmacology and therapeutics Vol. 82; no. 5; p. 525
• Main Authors: Bruck, H, Schwerdtfeger, T, Toliat, M, Leineweber, K, Heusch, G, Philipp, T, Nürnberg, P, Brodde, O-E
• Format: Journal Article
• Language: English
• Published: United States 01.11.2007
• Subjects: Adrenergic alpha-Agonists - administration & dosage; Adrenergic alpha-Agonists - pharmacology; Adult; Aging - metabolism; Blood Pressure - drug effects; Clonidine - administration & dosage; Clonidine - pharmacology; Female; Genotype; Heart Rate - drug effects; Humans; Injections, Intravenous; Male; Middle Aged; Norepinephrine - blood; Norepinephrine - secretion; Polymorphism, Genetic; Receptors, Adrenergic, alpha-2 - genetics; Receptors, Adrenergic, alpha-2 - metabolism
• ISSN: 1532-6535
• DOI: 10.1038/sj.clpt.6100181

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.