Regulation of carbachol‐ and histamine‐induced inositol phospholipid hydrolysis in a human oligodendroglioma

Abstract

A stable cell line derived from a human oligodendroglioma (HOG) was used to study the regulation of muscarinic- and histamine receptor-mediated phosphoinositide hydrolysis. Both carbachol and histamine increased inositol monophosphate (InsP) accumulation in a dose-and time-dependent manner in the presence of lithium and the effect of simultaneous addition of carbachol and histamine was additive, implying independent signal transduction pathways. Homologous desensitization of muscarinic, but not histamine receptors, could be demonstrated although neither receptor type appeared to be heterologously desensitized. [³H]InsP accumulation in HOG cells was also stimulated by fluoride, suggesting guanosine triphosphate (GTP)-binding protein involvement, but phosphoinositide (PtdIns) hydrolysis was not sensitive to pertussis toxin. Phorbol ester-activation of protein kinase C (PKC) inhibited both muscarinic and histamine receptor-stimulated InsP release but did not attenuate either the fluoride-induced release of InsP nor β-adrenergic receptor-mediated stimulation of adenylate cyclase activity. Taken together, we conclude that muscarinic and histamine receptors are differentially regulated through both PKC-dependent and -independent mechanisms, and that feedback inhibition of PtdIns turnover occurs proximal to the GTP binding proteins.