CALCIUM-SENSITIVE PARTICULATE GUANYLYL CYCLASE AS A MODULATOR OF CAMPIN OLFACTORY RECEPTOR NEURONS

The second messengers cAMP and inositol-1,4,5-triphosphate have been i mplicated in olfaction in various species. The odorant-induced cGMP re sponse was investigated using cilia preparations and olfactory primary cultures. Odorants cause a delayed and sustained elevation of cGMP. A component of this cGMP response is attributable to the activation of one of two kinetically distinct cilial receptor guanylyl cyclases by c alcium and a guanylyl cyclase-activating protein (GCAP). cGMP thus for med serves to augment the cAMP signal in a cGMP-dependent protein kina se (PKG) manner by direct activation of adenylate cyclase. cAMP, in tu rn, activates cAMP-dependent protein kinase (PKA) to negatively regula te guanylyl cyclase, limiting the cGMP signal. These data demonstrate the existence of a regulatory loop in which cGMP can augment a cAMP si gnal, and in turn cAMP negatively regulates cGMP production via PKA. T hus, a small, localized, odorant-induced cAMP response may be amplifie d to modulate downstream transduction enzymes or transcriptional event s.