GABA receptor-mediated effects in the peripheral nervous system: A cross-interaction with neuroactive steroids.

Abstract

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the adult mammalian central nervous system (CNS), exerts its action via an interaction with specific receptors (e.g., GABAA and GABAB). These receptors are expressed not only in neurons but also on glial cells of the CNS, which might represent a target for the allosteric action of neuroactive steroids. Herein, we have demonstrated first that in the peripheral nervous system (PNS), the sciatic nerve and myelin-producing Schwann cells express both GABAA and GABAB receptors. Specific ligands, muscimol and baclofen, respectively, control Schwann-cell proliferation and expression of some specific myelin proteins (i.e., glycoprotein P0 and peripheral myelin protein 22 [PMP22]). Moreover, the progesterone (P) metabolite allopregnanolone, acting via the GABAA receptor, can influence PMP22 synthesis. In addition, we demonstrate that P, dihydroprogesterone, and allopregnanolone influence the expression of GABAB subunits in Schwann cells. The results suggest, at least in the myelinating cells of the PNS, a cross-interaction within the GABAergic receptor system, via GABAA and GABAB receptors and neuroactive steroids.