Receptor-mediated phosphoinositide metabolism in peripheral nerve and cultured Schwann cells

Abstract

Peripheral nerve possesses muscarinic cholinergic receptors, predominantly of the M₃ 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)triphosphate-stimulated hydrolysis of exogenous phosphatidylinositol-4,5-bis-phosphate that is blocked by atropine can be reconstituted in a purified peripheral myelin-rich fraction. Nerve phosphoinositide turnover is also stimulated by adenosine analogs and blocked by adenosine receptor antagonists in a pattern consistent with the presence of adenosine A₂ receptors in the tissue. Receptor-mediated phosphoinositide metabolism has also been studied in a human tumor-derived Schwann cell line (NF1T) derived from a neurofibromatosis-1 patient. By the same experimental criteria, NF1T cells also appear to contain adenosine A₂ receptors which upon activation stimulate phosphoinositide turnover. However, phosphoinositide metabolism in these cells is not increased by either carbachol or ATP. Our findings taken together with other reports suggest that Schwann cells may possess a variety of receptors which regulate phosphoinositide metabolism.