We show that calmodulin-dependent phosphodiesterase (CAM-PDE) is selectively expressed in mature olfactory receptor neurons within the olfactory mucosa. Immunocytochemical staining reveals neuronal immunoreactivity that is most pronounced within cilia, dendritic knobs, and axon bundles. Neither sustentacular cells nor basal cells display immunoreactivity. The extent of loss of neuronal immunoreactivity following bulbectomy resembles loss of the neuronal population. High-affinity CAM-PDE activity in olfactory cilia is fivefold greater than in brain, when assayed at low micromolar cAMP. This activity is depleted in turbinates following bulbectomy. Olfactory mucosal PDE activity is composed of a minimum of two major forms. In the absence of Ca(2+), rolipram-sensitive PDE comprises 65% of total activity. Following stimulation by Ca2+, CAM-PDE activity is elevated sixfold to become the predominant form, thereby increasing total activity 300%, with half-maximal effect at 1 microM Ca2+. We propose that Ca2+ stimulation of CAM-PDE may be necessary for termination of olfactory signals.
Although the CAMP and phosphoinositide (PI) second messenger systems are involved in olfactory signal transduction, aspects of their roles remain unclear. We have further examined the rapid kinetics of CAMP fluctuations in response to odorants in rat olfactory cilia isolated by calcium shock. Odorants cause a rapid and transient subsecond elevation of CAMP levels, as well as a more sustained signal lasting 5-10 sec. Basal CAMP levels demonstrate a biphasic calcium dependence; calcium enhanced both adenylyl cyclase (AC) and phosphodiesterase (PDE) activities. The odorantinduced CAMP response also demonstrated a biphasic dependence on calcium, with peak activity at 10 MM free calcium. All odorants tested were found to stimulate CAMP accumulation, and the dose-response curves were multiphasic, with less stimulation seen at higher concentrations. Dose-response curves performed for isovaleric acid at two free calcium concentrations demonstrated that calcium can influence cellular responsiveness to odorants and may be involved with signal potentiation as well as desensitization.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.