RECEPTOR-MEDIATED PHOSPHOINOSITIDE METABOLISM IN PERIPHERAL-NERVE ANDCULTURED SCHWANN-CELLS

Peripheral nerve possesses muscarinic cholinergic receptors, predomina ntly of the M(3) subtype, that stimulate phosphoinositide metabolism. Evidence suggests that one site of this response is the myelin sheath. Purified peripheral nerve myelin contains several heterotrimeric GTP- binding proteins. Furthermore, carbachol and guanosine-5'-(3-O-thio)tr iphosphate-stimulated hydrolysis of exogenous phosphatidylinositol-4,5 -bis-phosphate that is blocked by atropine can be reconstituted in a p urified peripheral myelin-rich fraction. Nerve phosphoinositide turnov er is also stimulated by adenosine analogs and blocked by adenosine re ceptor antagonists in a pattern consistent with the presence of adenos ine A(2) receptors in the tissue. Receptor-mediated phosphoinositide m etabolism has also been studied in a human tumor-derived Schwann cell line (NF1T) derived from a neurofibromatosis-1 patient. By the same ex perimental criteria, NF1T cells also appear to contain adenosine A(2) receptors which upon activation stimulate phosphoinositide turnover. H owever, phosphoinositide metabolism in these cells is not increased by either carbachol or ATP. Our findings taken together with other repor ts suggest that Schwann cells may possess a variety of receptors which regulate phosphoinositide metabolism.