Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study we investigated the influence of phentolamine and the phenothiazine compounds chlorpromazine and trifluoperazine on human platelet aggregation as well as the effect of the association of phentolamine and the phenothiazines on responses to adenosine diphosphate, collagen, thrombin, ionophore A23187 and phorbol-myristate acetate, release reaction, thromboxane B2 synthesis and intraplatelet cyclic adenosine monophosphate levels. Phentolamine and phenothiazines exerted a dose-dependent inhibitory effect on aggregation induced by different concentrations of adenosine diphosphate and decreased the response to other agonists; furthermore, the phenothiazines enhanced the inhibitory effects of phentolamine on aggregation and thromboxane B2 synthesis, without influencing intraplatelet cyclic adenosine monophosphate levels. Phorbol ester-induced platelet activation was also inhibited in a dose-dependent way by each compound and by an association of phentolamine and phenothiazines, suggesting that the antiplatelet properties of these compounds might also be ascribed to intracellular events.
 ...
PMID:Phenothiazine compounds enhance phentolamine effects on platelet aggregation and thromboxane B2 production. 198 77

The present study was undertaken to clarify the underlying mechanisms responsible for contractions of isolated coronary arteries and aortae from rabbits in response to thrombin-stimulated autologous platelets. Thrombin-stimulated platelets evoked potent contractions of both arteries in a platelet concentration-related manner. Pretreatment of platelets with aspirin, which almost completely inhibited thromboxane A2 synthesis but not the release reaction of biologic monoamines from platelets, caused only slight suppression of platelet-induced contractions of both arteries. Ketanserin as well as methysergide markedly inhibited aortic contractions to platelets. In contrast, the contractile responses of coronary arteries to platelets were suppressed by methysergide but not by ketanserin. Pretreatment of the arteries with diphenhydramine did not inhibit the aortic responses to platelets, but significantly suppressed coronary arterial contractions induced by higher concentrations of platelets. Phentolamine had no inhibitory effects on the responses of either artery to platelets. Pretreatment of arteries with aspirin did not affect the contractile responses of either artery to platelets. The contractile responses of aortae to exogenously administered serotonin were competitively antagonized by ketanserin, but those of coronary arteries were not. Coronary contractions to serotonin were competitively inhibited by methiothepin and significantly suppressed by methysergide. The contractile responses of both arteries to histamine were antagonized by diphenhydramine but not by cimetidine. On the basis of our results obtained from studies in organ chamber, we conclude that a major role of thromboxane A2 was not demonstrated in platelet-induced contractions of the arteries, and that those of aortae were mainly mediated by platelet-derived serotonin at S2 receptor and those of coronary arteries at S1-like receptor. The contractions of coronary arteries in responses to higher concentrations of platelets were partly mediated by histamine at H1 receptor.
 ...
PMID:Role of serotonin, histamine, and thromboxane A2 in platelet-induced contractions of coronary arteries and aortae from rabbits. 247 28

The secretory status of mast cells of mesentery and subcutaneous connective tissue was studied in rats using the morphometry analysis. Immobilization for 30 min has induced a 3.7-fold decrease of the heparin saturation index in these mast cells and a 3-fold increase of the granulolysis index. In rats preliminary given propranolol, alpha-adrenoceptor antagonist (1.25 mg/kg), a stimulatory effect of immobilization was absent. Phentolamine, alpha-adrenoceptor antagonist (6 mg/kg), partially inhibited the immobilization effect. Isoprenaline, beta-agonist (1.5 mg/kg), activated heparin secretion in rats without immobilization, while phenylephrine, alpha-agonist (2.5 mg/kg) had no effect on the secretory state of mast cells. Propranolol in the same dose also blocked the stimulatory action of i. v. injected alpha-thrombin (50 NIH/kg) on heparin secretion from mast cells of subcutaneous connective tissue. The obtained results show that catecholamines participate in activation of heparin release from mast cells induced both by the stress and by thrombin injection. Their action is mediated by beta-adrenoceptors of the vessel wall.
 ...
PMID:[Role of catecholamines, released due to stress, on stimulation of heparin secretion by mast cells in rats]. 824 16

The modulation of the production of prostacyclin and thromboxane from cat and cat aortic tissue slices by different vasoactive agents has been studied in order to reveal whether the release of these main two vasoactive prostanoids goes in parallel or may be controlled independently. Norepinephrine, isoproterenol, phentolamine, propranolol, angiotensin II, vasopressin, bradykinin, thrombin, verapamil, gallopamil, dopamine or methionin enkephalin were added to the incubation medium and 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) and TxB2 (the stable metabolite of thromboxane) were determined in the supernatant by radioimmunoassay. The ratio of the release of prostacyclin and thromboxane was computed. Norepinephrine increased both prostacyclin and thromboxane release. Isoproterenol increased the ratio of prostacyclin and thromboxane released in cat aortic tissue slices. Phentolamine and propranolol had no effects. Angiotensin II induced a slight but statistically insignificant increase in the ratio of the two prostanoids released. Vasopressin increased thromboxane release only. Bradykinin stimulated the prostacyclin while thrombin stimulated the thromboxane release. Verapamil decreased both prostacyclin and thromboxane production. Gallopamil decreased prostacyclin release and increased thromboxane release from vessel wall slices in a certain concentration range causing a characteristic dose dependent minimum in the ratio of prostacyclin and thromboxane release. Dopamine separately increased prostacyclin release while enkephalin had no significant effect. The data obtained show that in vascular tissue some unidentified yet cytophysiological mechanisms might exist which specifically control the activities of the prostacyclin synthase and thromboxane synthase enzymes.
 ...
PMID:Prostacyclin and thromboxane production of rat and cat arterial tissue is altered independently by several vasoactive substances. 890 22