Cross-talk between olfactory second messenger pathways

The second messengers 3'-5'-cyclic-monophosphate (cAMP) and inositol 1,4,5- trisphosphate (InsP(3)) have been implicated in olfactory signal transducti on in various species. The results of the present study provide evidence th at the two olfactory second messenger pathways in rat olfactory neurons do not work independently but rather show a functional antagonism: whereas inh ibition of phospholipase C (PLC) in isolated olfactory cilia by U-73122 led to an augmentation of odor-induced cAMP signaling, activation of the phosp hoinositol pathway resulted in attenuation of odor-induced cAMP formation. Furthermore, this study indicates that elevated cAMP levels cause suppressi on of odor-induced InsP(3) signaling, whereas inhibition of adenylate cycla se (AC) by cisN-(2-phenylcyclopentyl)azacylotridec-1-en-2-amine (MDL-12,330 A) results in potentiation of odor-induced InsP(3) formation. Concerning t he molecular mechanism involved in cross-interaction, the experimental data indicate that the observed antagonism of elevated cAMP is based on inhibit ion of PLC activation rather than on stimulation of InsP(3) degradation. As blockage of the endogenous protein kinase A (PKA) prevented the inhibitory effect of cAMP, the suppression of odor-induced InsP(3) signaling by cAMP may be mediated by a PKA-controlled reaction.