Functional characterization of the α-adrenoceptor in adult male rat locus coeruleus neurons .

INTRODUCTION

The α-adrenoceptor (αAR) is involved in the physiopathology of the central nervous system (CNS), but its function in the adult male rat locus coeruleus (LC) has not been fully studied. We aimed to characterize the role of the αAR in the regulation of the firing rate (FR) of LC neurons and to describe the signaling pathways involved.

METHODS

We measured, through single-unit extracellular recordings of LC neurons from adult male rats were used to measure the effect of adrenergic agonists in the presence and absence of adrenergic antagonists or inhibitors of several signalling pathways.

RESULTS

Noradrenaline (NA) (100 µM) and phenylephrine (PE) (100 µM) induced a stimulatory effect in the presence of α-adrenoceptor (αAR) antagonist RS 79948 (0.1 µM). The αAR agonist cirazoline (1-100 µM) also stimulated the FR of LC neurons. The stimulatory effects of NA (100 µM), PE (100 µM), and cirazoline (1 μM and 10 µM) were blocked by αAR antagonist WB 4101 (0.5 µM). NA (100 µM)-induced stimulation was reduced in the presence of G protein inactivator pertussis toxin (PTX) (500 ng ml) and the transient receptor potential (TRP) channel blocker 2-APB (30 µM), but not by protein kinase C (PKC) inhibitor Go 6976 (1 µM), G protein-activated inward rectifier potassium (GIRK) channel blocker BaCl (300 µM), or protein kinase A (PKA) inhibitor H-89 (10 µM). The stimulatory effect of cirazoline was not reduced by any of the tested inhibitors.

CONCLUSIONS

From αAR activation stimulates the FR of adult rat LC neurons through a signaling pathway that involves G proteins and TRP channels.