scholarly journals Platelet activating factor and U44069 stimulate a GTPase activity in human platelets which is distinct from the guanine nucleotide regulatory proteins, Ns and Ni

1986 ◽  
Vol 234 (3) ◽  
pp. 737-740 ◽  
Author(s):  
M D Houslay ◽  
D Bojanic ◽  
A Wilson
Keyword(s):  
Regulatory Protein ◽  
Platelet Activating Factor ◽  
Phospholipid Metabolism ◽  
Human Platelets ◽  
Regulatory Proteins ◽  
Guanine Nucleotide ◽  
Gtpase Activity ◽  
Guanine Nucleotide Regulatory Proteins ◽  
Gtpase Activation ◽  
Guanine Nucleotide Regulatory Protein

Platelet-activating factor (PAF, 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine) and the stable thromboxane-receptor agonist U44069 (9 alpha, 11 beta-epoxymethanoprostaglandin H2) stimulated GTPase activity in platelet membranes in a dose-dependent fashion, yielding Ka values of 12 nM and 27 nM respectively. The degree of GTPase activation elicited by these agents was found to be additive with the GTPase activation due to either the stimulatory (Ns) or inhibitory (Ni) guanine nucleotide regulatory proteins when activated by prostaglandin E1 and adrenaline (+propranolol) respectively. Treatment of membranes with either cholera or pertussis toxins, which inhibited markedly the receptor-mediated stimulation of the GTPase activities of Ns and Ni respectively, had no or only a small effect, respectively, on the GTPase activity stimulated by PAF and U44069. It is suggested that PAF and U44069, which stimulate inositol phospholipid metabolism in platelets, exert actions through a guanine nucleotide regulatory protein which is distinct from Ns and Ni.

scholarly journals Thrombin, unlike vasopressin, appears to stimulate two distinct guanine nucleotide regulatory proteins in human platelets

1986 ◽  
Vol 238 (1) ◽  
pp. 109-113 ◽  
Author(s):  
M D Houslay ◽  
D Bojanic ◽  
D Gawler ◽  
S O'Hagan ◽  
A Wilson
Keyword(s):  
Pertussis Toxin ◽  
Plasma Membranes ◽  
Regulatory Protein ◽  
Platelet Activating Factor ◽  
Phospholipid Metabolism ◽  
Human Platelets ◽  
Regulatory Proteins ◽  
Guanine Nucleotide ◽  
Gtpase Activity ◽  
Guanine Nucleotide Regulatory Protein

The thrombin-stimulated GTPase activity of human platelets was additive with respect to the GTPase stimulation effected by prostaglandin E1, but not with that stimulated by adrenaline, vasopressin and platelet-activating factor (PAF). Treatment of platelet membranes with pertussis toxin partially inhibited the thrombin-stimulated GTPase, but had no effect on the vasopressin-stimulated GTPase activity, whereas cholera toxin treatment had no effect on either of these stimulated GTPase activities. Thrombin, adrenaline and PAF, but not vasopressin, inhibited the adenylate cyclase activity of isolated plasma membranes through the action of Ni only, this being inhibited by pertussis toxin. It is suggested that thrombin exerts effects through both the inhibitory guanine nucleotide regulatory protein Ni and through the putative guanine nucleotide regulatory protein, Np, involved in regulating receptor-stimulated inositol phospholipid metabolism. However, vasopressin appears to exert its effects solely through the putative Np.

scholarly journals Glucagon desensitization of adenylate cyclase and stimulation of inositol phospholipid metabolism does not involve the inhibitory guanine nucleotide regulatory protein Gi, which is inactivated upon challenge of hepatocytes with glucagon

1989 ◽  
Vol 259 (1) ◽  
pp. 191-197 ◽  
Author(s):  
G J Murphy ◽  
D J Gawler ◽  
G Milligan ◽  
M J O Wakelam ◽  
N J Pyne ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
G Protein ◽  
Pertussis Toxin ◽  
Plasma Membranes ◽  
Inositol Phosphates ◽  
Regulatory Protein ◽  
Phospholipid Metabolism ◽  
Guanine Nucleotide ◽  
Inositol Phospholipid ◽  
Guanine Nucleotide Regulatory Protein

Brief exposure of hepatocytes to glucagon, angiotensin or the protein kinase C activator TPA (12-O-tetradecanoylphorbol 13-acetate) caused the inactivation of the inhibitory guanine nucleotide regulatory protein Gi. Glucagon-mediated desensitization of glucagon-stimulated adenylate cyclase activity was seen in hepatocytes from both normal rats and those made diabetic with streptozotocin, where Gi is not functionally expressed. Normal glucagon desensitization was seen in hepatocytes from young animals, 6 weeks of age, which had amounts of Gi in their hepatocyte membranes which were some 45% of that seen in mature animals (3.4 pmol/mg of plasma-membrane protein). Streptozotocin-induced diabetes in young animals abolished the appearance of functional Gi in hepatocyte plasma membranes. Pertussis-toxin treatment of hepatocytes from both normal mature animals and those made diabetic, with streptozotocin, blocked the ability of glucagon or angiotensin or TPA to elicit desensitization of adenylate cyclase. The isolated B (binding)-subunit of pertussis toxin was ineffective in blocking desensitization. Neither induction of diabetes nor treatment of hepatocytes with pertussis toxin inhibited the ability of glucagon and angiotensin to stimulate the production of inositol phosphates in intact hepatocytes. Thus (i) Gi does not appear to play a role in the molecular mechanism of glucagon desensitization in hepatocytes, (ii) the G-protein concerned with receptor-stimulated inositol phospholipid metabolism in hepatocytes appears not to be a substrate for the action of pertussis toxin, (iii) in intact hepatocytes, treatment with glucagon and/or angiotensin can elicit the inactivation of the inhibitory G-protein Gi, and (iv) pertussis toxin blocks desensitization by a process which does not involve Gi.

Effects of cations on binding of human choriogonadotropin

1988 ◽  
Vol 66 (12) ◽  
pp. 1258-1264
Author(s):  
Patrick J. McIlroy
Keyword(s):  
Binding Sites ◽  
Regulatory Protein ◽  
Guanine Nucleotides ◽  
Guanine Nucleotide ◽  
Human Choriogonadotropin ◽  
Receptor Sites ◽  
Number Of Binding Sites ◽  
Receptor Number ◽  
Guanine Nucleotide Regulatory Protein ◽  
Low Ionic Strength

The effect of various salts on the binding of human choriogonadotropin to rat luteal membranes has been examined. Increasing salt concentrations had biphasic effects, initially increasing binding, then decreasing it. With NaCl, these effects were on both the affinity and the number of receptor sites. The affinity increased with increasing NaCl concentrations, to a maximum at 40 mM, and then decreased. Above 40 mM NaCl, the number of binding sites increased. NaCl also altered the effects of Mg2+ and guanyl nucleotides. At low ionic strength, Mg2+ was necessary to observe binding. Guanine nucleotides modulated this binding by decreasing the affinity. At 40 mM NaCl, Mg2+ increased receptor number without altering affinity. Guanyl nucleotides modulated this binding by reducing the number of sites to that observed in the absence of Mg2+. At 150 mM NaCl, Mg2+ and guanine nucleotides had no effect. The results suggest the presence of two pools of human choriogonadotropin receptor in rat corpus luteum, one coupled to the guanine nucleotide regulatory protein (Ns) and being Mg2+ dependent and guanine nucleotide sensitive, and the other not coupled to Ns and being Mg2+ independent and guanine nucleotide insensitive.

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