NEURONAL NICOTINIC RECEPTOR EXPRESSION IN SENSORY NEURONS OF THE RAT TRIGEMINAL GANGLION - DEMONSTRATION OF ALPHA-3-BETA-4, A NOVEL SUBTYPEIN THE MAMMALIAN NERVOUS-SYSTEM

The identification of a family of neuronal nicotinic receptor subunit genes establishes the potential for multiple subtypes with diverse phy siological functions. Virtually all of the high affinity nicotinic rec eptors measured to date in the rodent CNS are composed of alpha 4 and beta 2 subunits only. However, the demonstration of other subunit tran scripts in a variety of central and peripheral nervous tissues suggest s a greater degree of receptor subtype heterogeneity than so far has b een elucidated. The purpose of the present studies was to determine at the mRNA and protein levels which neuronal nicotinic receptor subunit s are expressed by sensory neurons of the rat trigeminal ganglion and in what combinations these gene products associate to form neuronal ni cotinic receptor subtypes in this tissue. Radioreceptor binding analys is indicated that in the adult rat trigeminal ganglion there exist at least two nicotinic receptor binding sites with differing affinities f or [H-3]-epibatidine. In situ hybridization histochemical studies reve aled the existence of mRNA encoding the alpha 3, alpha 4, alpha 5, bet a 2, and beta 4 subunits, but not the alpha 2 subunit. Immunoprecipita tion with subunit-specific antisera demonstrated that each of the subu nits present in the ganglion at the mRNA level is a constituent of nic otinic receptors capable of binding H-3-epibatidine. Various applicati ons of these approaches yielded strong evidence that, in addition to a lpha 4 beta 2, which is thought to be the predominant neuronal nicotin ic receptor subtype in the rodent CNS, trigeminal sensory neurons expr ess as the principal subtype alpha 3 beta 4, which has not been demons trated previously in mammalian nervous tissue.