Receptor-Effector Coupling in Platelets: Roles of Guanine Nucleotides

Effect of various excitatory agonists on the secretion of 5‐hydroxytryptamine from permeabilised human platelets induced by Ca2+ in the presence or absence of GTP

“…la) which has a much higher efficacy for both 1,2-diacylglycerol synthesis [12,13] and for phosphatidate [9] synthesis. The results previously obtained for the effects of vasopressin, PAF and U-46619 also accord with this correlation since these agonists cause both phosphatidate synthesis [9] and enhancement of Ca*+-dependent [14C]5HT secretion [4,5] at a level which is intermediate between that observed on stimulation by thrombin and by 5HT.…”

“…Recently a guanine nucleotide binding protein has been implicated in receptor-phospholipase C coupling on the basis that addition of micromolar concentrations of GTP enhance the stimulation of Shydroxytryptamine (5HT) secretion caused by thrombin or PAF in the presence of non-saturating concentrations of Ca2+ and that such stimulation can also be observed on addition of nonhydrolysable analogues of GTP in the absence of an excitatory agonist [4,5].…”

“…Addition of thrombin causes a shift to the left in the dose/response curve for secretion from the amine storage granules induced by Ca2+ in this preparation without increasing the maximal extent of this response [2,3]. A similar but smaller shift results from addition of vasopressin, 11,9-epoxymethanoprostaglandin HZ (U-46619) or platelet-activating factor (PAF) [4,5]. Addition of thrombin enhances the maximal extent of lysosomal secretion induced by Ca2+ without causing a significant shift in the dose/response curve [6].…”

Antagonism of the platelet activating factor‐induced rise of the intracellular calcium ion concentration of U937 cells

“…(Haslam et al, 1985;Lad et al, 1985;Hwang et al, 1986). An investigation into the mechanism of stimulus-response coupling in U937 cells, especially with respect to the guanyl nucleotide regulatory proteins and polyphosphoinositol metabolism (Berridge & Irvine, 1984), may elucidate the mechanism by which Paf interacts with plasma membrane receptors to induce calcium mobilisation.…”