Expression and functional activity of proteinase-activated receptors 1 and 2 in the rat olfactory

Alterations in the olfactory system and impairment of olfactory function occurr in neurodegenerative diseases, such as Alzheimer’ s and Parkinson’ s diseases. The participation of proteinase-activated receptors (PARs) in these conditions has been postulated, but little is known on the expression and activity of PARs in the olfactory system. We investigated the presence, the signaling properties and cellular actions of PAR1 and PAR2 in the rat main olfactory bulb and in primary cultures of olfactory bulb and olfactory sensory neurons. PAR1 and PAR2 activity was predominantly expressed in the olfactoty nerve-glomerular cell layer (ON-GL), where selective peptide agonists inhibited cyclic AMP formation and stimulated [35S ]GTPyS binding, phosphoinositide hydrolysis, CaMKII phosphorylation and Rho activation. Nanomolar concentrations of thrombin and trypsin mimicked the actions of the peptide agonists. Lesion of the olfactory mucosa caused a reduction of PAR1 and PAR2 activity in ON-GL, suggesting the possible localization of a receptor population on olfactory nerve terminals. In primary cultures of olfactory bulb cells and olfactory neuroepithelial cells, exposure to either serine proteinases or selective peptide agonists caused a rapid neurite retraction. Immunofluorescence analysis showed the presence of PAR1 and PAR2 in neurons and glial cells of olfactory bulb and in olfactory sensory neurons. These data provide the first evidence that PAR1 and PAR2 are expressed and functional in different structures of the olfactory system and suggest the possible involvement of the receptor in neurodegenerative processes affecting the olfactory function.