Functional characterization of the α 1 -adrenoceptor in adult male rat locus coeruleus neurons ex vivo

Irati RodillaAitziber Mendiguren^*Joseba Pineda

• Department of Pharmacology, Faculty of Medicine and Nursing. University of the Basque Country, Leioa, Spain

α1-adrenoceptor (α1AR) is involved in the physiopathology of the CNS, but its function in the adult male rat locus coeruleus (LC) has not been fully studied. We aimed to characterize the role of α1AR in the regulation of the firing rate (FR) of LC neurons, and to describe the signalling pathways involved. We measured, by single-unit extracellular recordings of LC neurons from adult male rats, the effect of adrenergic agonists in the presence and absence of adrenergic antagonists and/or inhibitors of several signalling pathways. Noradrenaline (NA) (100 µM) and phenylephrine (PE) (100 µM) induced a stimulatory effect in the presence of the α2-adrenoceptor (α2AR) antagonist RS 79948 (0.1 µM). The α1AR agonist cirazoline (1-100 µM) also stimulated the FR of LC neurons. The stimulatory effects of NA (100 µM), PE (100 µM) and cirazoline (10 µM) were blocked by the α1AR antagonist WB 4101 (0.5 µM). NA (100 µM)-induced stimulation was reduced in the presence of Gi/o protein inactivator pertussis toxin (PTX) (500 ng·ml-1) and transient receptor potential (TRP) channels blocker 2-APB (30 µM), but not by the PKC inhibitor Go 6976 (1 µM), G protein-activated inward rectifier potassium (GIRK) channel blocker BaCl2 (300 µM) or the PKA inhibitor H-89 (10 µM). The stimulatory effect of cirazoline was not reduced by any of the tested inhibitors. α1AR activation stimulates the FR of adult rat LC neurons through a signalling pathway that involves Gi/o proteins and TRP channels.