Endothelin influences pHi of human platelets through protein kinase C mediated pathways

Touyz, R.M. , Larivière, R. and Schiffrin, E.L. (1995) Endothelin influences pHi of human platelets through protein kinase C mediated pathways. Thrombosis Research, 78(1), pp. 55-65. (doi: 10.1016/0049-3848(95)00034-8)

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Stimulation of human platelets with endothelin raises cytosolic pH (pH<sub>i</sub>). In order to determine whether this effect is mediated via protein kinase C and Na+-H+ linked pathways, the effects of staurosporine and calphostin C (protein kinase C inhibitors) and 5-(N,N-hexamethylene) amiloride (Na+-H+ exchange blocker) on endothelin-induced pHi responses in human platelets were assessed. In addition, platelet endothelin receptor subtypes were determined pharmacologically using the selective ETA receptor antagonist BQ-123 and the ETB receptor agonist sarafotoxin S6c. pHi was measured spectrofluorometrically using the fluorescent probe BCECF-AM in platelets obtained from 15 healthy subjects. Endothelin-1 at a fixed concentration of 10−9 M significantly increased pH<sub>i</sub> from 7.11 ± 0.01 ([H+]i = 77 ± 0.9 nM) to 7.19 ± 0.04 ([H+]i = 64 ± 0.9 nM) (p<0.01). The pHi-stimulating effect of endothelin-1 was inhibited by 10−7 M staurosporine, calphostin C and 5-(N,N-hexamethylene) amiloride. BQ-123 (10−7 M) abolished the pHi responses to endothelin-1, whereas sarafotoxin S6c had no effect on platelet pHi. These data suggest that in vitro effects of endothelin-1 on platelet pH<sub>i</sub> are receptor-mediated via a pathway involving protein kinase C. Platelet endothelin receptors appear to be of the ET<sub>A</sub> subtype.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Touyz, R.M., Larivière, R., and Schiffrin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Thrombosis Research

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