INVOLVEMENT OF NONMUSCARINIC RECEPTORS IN PHOSPHOINOSITIDE SIGNALING DURING SOMAN-INDUCED SEIZURES

Previous investigations have indicated that soman-induced convulsions involve the inositol lipid signalling system. We previously reported t hat 10 min after the onset of seizures, inositol 1,4,5-triphosphate (I P3) build-up was coupled to activation of non-muscarinic receptor subt ypes. In the present study, we demonstrate that (1) in addition to mus carinic receptors, histamine H-1 subtypes and glutamate metabotropic r eceptors contribute to the first IP3 increase (first 10 min of seizure s) and (2) the histamine H-1 subtype and glutamate metabotropic recept ors are also involved in the second step of inositol phosphate respons e (after 10 min of seizures). alpha(1)-adrenoceptor and 5-HT2 receptor s, known to be coupled to phosphoinositide turnover, did not participa te in soman-induced IP3 response. Neurochemical interactions between c holinergic, histamine H-1 and glutamate metabotropic systems, responsi ble of the phosphoinositide hydrolysis under soman are envisaged.