ODORANTS SELECTIVELY ACTIVATE DISTINCT G-PROTEIN SUBTYPES IN OLFACTORY CILIA

Chemoelectrical signal transduction in olfactory neurons appears to in volve intracellular reaction cascades mediated by heterotrimeric GTP-b inding proteins. In this study attempts were made to identify the G pr otein subtype(s) in olfactory cilia that are activated by the primary (odorant) signal. Antibodies directed against the alpha subunits of di stinct G protein subtypes interfered specifically with second messenge r reponses elicited by defined subsets of odorants; odor-induced cAMP- formation was attenuated by G alpha(s) antibodies, whereas G alpha(o) antibodies blocked odor-induced inositol 1,4,5-trisphosphate (IP3) for mation. Activation-dependent photolabeling of G alpha subunits with [a lpha-(32)p]GTP azidoanilide followed by immunoprecipitation using subt ype-specific antibodies enabled identification of particular individua l G protein subtypes that were activated upon stimulation of isolated olfactory cilia by chemically distinct odorants, For example odorants that elicited a cAMP response resulted in labeling of a G alpha(s)-lik e protein, whereas odorants that elicited an IP3 response led to the l abeling of a G alpha(o)-like protein. Since odorant-induced IP3 format ion was also blocked by G(beta) antibodies, activation of olfactory ph ospholipase C might be mediated by beta gamma subunits of a G(o)-like G protein. These results indicate that different subsets of odorants s electively trigger distinct reaction cascades and provide evidence for dual transduction pathways in olfactory signaling.