Guanosine-5′-(3-O-thio)triphosphate-mediated stimulation of phosphoinositidase C in solubilized rat peripheral nerve myelin and its alteration in streptozotocin induced diabetes
✍ Scribed by J. Mathew; J. Eichberg
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 780 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
The regulation of phosphoinositidase C (PIC) activity by guanosine-5'-(3-O-thio)triphosphate (GTPyS) 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-4,5bisphosphate (PIP,) in a dose-dependent manner only within a narrow range of cholate concentrations. Maximal stimulation was attained at 0.6 pM GTPyS and could be completely prevented by 1 pM guanosine-5'-(2-O-thio)diphosphate. Neither adenylyl-imidodiphosphate nor adenosine triphosphate (ATP) enhanced PIC activity. Carbamoylcholine (1 mM) added together with GTPyS increased the extent of PIP, hydrolysis over that elicited by GTPyS alone and this stimulation was blocked by the muscarinic receptor antagonist, atropine (50 pM). In detergentsolubilized myelin preparations from streptozotocininduced diabetic rats, a higher concentration of the guanine nucleotide analog 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.