Two alpha(2)-adrenergic receptor subtypes, alpha(2A) and alpha(2C), inhibit transmitter release in the brain of gene-targeted mice

Neuroscience
M M BüchelerL Hein

Abstract

alpha(2)-Adrenergic receptors play an essential role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the CNS. However, the role of each of the three highly homologous alpha(2)-adrenergic receptor subtypes (alpha(2A), alpha(2B), alpha(2C)) in this process has not been determined unequivocally. To address this question, the regulation of norepinephrine and dopamine release was studied in mice carrying deletions in the genes encoding the three alpha(2)-adrenergic receptor subtypes. Autoradiography and radioligand binding studies showed that alpha(2)-receptor density in alpha(2A)-deficient brains was decreased to 9 +/- 1% of the respective wild-type value, whereas alpha(2)-receptor levels were reduced to 83 +/- 4% in alpha(2C)-deficient mice. These results indicate that approximately 90% of mouse brain alpha(2)-receptors belong to the alpha(2A) subtype and 10% are alpha(2C)-receptors. In isolated brain cortex slices from wild-type mice a non-subtype-selective alpha(2)-receptor agonist inhibited release of [(3)H]norepinephrine by maximally 96%. Similarly, release of [(3)H]dopamine from isolated basal ganglion slices was inhibited by 76% by an alpha(2)-receptor agonist. In alpha(2A)-recep...Continue Reading

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Citations

Aug 10, 2006·Cell and Tissue Research·Lutz Hein
Jan 17, 2004·Chemico-biological Interactions·Maria KonstandiMatti A Lang
Aug 21, 2003·Progress in Neurobiology·Mark J Millan
Feb 4, 2014·Psychopharmacology·Jan BrosdaHeinz H Pertz
Jan 21, 2012·ChemMedChem·Eric JnoffCéline Vermeiren
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