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Guanosine‐5′‐(3‐O‐thio)triphosphate‐mediated stimulation of phosphoinositidase C in solubilized rat peripheral nerve myelin and its alteration in streptozotocin induced diabetes
Author(s) -
Mathew J.,
Eichberg J.
Publication year - 1994
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490370111
Subject(s) - stimulation , guanosine , streptozotocin , myelin , diabetes mellitus , pharmacology , endocrinology , chemistry , medicine , thio , biochemistry , central nervous system , stereochemistry
The regulation of phosphoinositidase C (PIC) activity by guanosine‐5′‐(3‐O‐thio)triphosphate (GTPγgMS) was characterized in a cholate‐solubilized peripheral myelin‐enriched fraction from rat sciatic nerve. The GTP analog maximally enhanced PIC‐catalyzed hydrolysis of exogenous phosphatidylinositol‐4,‐5‐bisphosphate (PIP 2 ) in a dose‐dependent manner only within a narrow range of cholate concentrations. Maximal stimulation was attained at 0.6 μM GTPγS and could be completely prevented by 1 μM guanosine‐5′‐(2‐O‐thio)diphosphate. Neither adenylyl‐imidodiphosphate nor adenosine triphosphate (ATP) enhanced PIC activity. Carbamoylcholine (1 mM)added together with GTPγS increased the extent of PIP 2 hydrolysis over that elicited by GTPγ increased the extent of PIP 2 hydrolysis over that elicited by GTPγS alone and this stimulation was blocked by the muscarinic receptor antagonist, atropine (50 μM). In detergent solubilized myelin preparations from streptozotocin induced diabetic rats, a higher concentration of the guanine nucleotide analogn was required to achieve stimulation comparable to that obtained with corresponding preparations from normal animals. These results suggest that sciatic nerve myelin possesses muscarinic receptors coupled via a GTP‐binding protein to PIC and that this system can be reconstituted in detergent‐solubilized extracts. It is possible that the function of G Proteins in cell signaling is impaired in experimental diabetic neuropathy. © 1994 Wiley‐Liss, Inc.