ABSTRACT
Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.
Subject(s)
Humans , Diltiazem/pharmacology , Dose-Response Relationship, Drug , Drug Synergism , Estrenes/pharmacology , Flavones/pharmacology , In Vitro Techniques , Indomethacin/pharmacology , Kinetics , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation/drug effects , Platelet Activating Factor/pharmacology , Platelet Activation/drug effects , Platelet Aggregation/drug effects , Pyrrolidinones/pharmacology , Serotonin/pharmacology , Thromboxane A2/biosynthesis , Verapamil/pharmacologyABSTRACT
Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.
Subject(s)
Humans , Diltiazem/pharmacology , Dose-Response Relationship, Drug , Drug Synergism , Estrenes/pharmacology , Flavones/pharmacology , In Vitro Techniques , Indomethacin/pharmacology , Kinetics , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation/drug effects , Platelet Activating Factor/pharmacology , Platelet Activation/drug effects , Platelet Aggregation/drug effects , Pyrrolidinones/pharmacology , Serotonin/pharmacology , Thromboxane A2/biosynthesis , Verapamil/pharmacologyABSTRACT
OBJECTIVE: To compare the tolerability and efficacy of salbutamol and theophylline in treating wheezy infant. DESIGN: This was a prospective parallel group study. SETTING AND SUBJECTS: Wheezy infants admitted in paediatric ward of Khulna Medical College Hospital from January 1998 to March 1999. MAIN OUTCOME VARIABLES: Palatability of drugs, clinical efficacy of drugs and adverse events during treatment. Ninety-five patients had undergone this study. Forty eight were was in salbutamol group and 47 in theophylline group. Clinical problem at the beginning was recurrent wheeze [46.3%], wheeze with fever [32.6%] and spasmodic cough [21.1%]. Salbutamol was more palatable [P < 0.001] than theophylline. However efficacy of both the drugs were nearly equal [P > 0.1]. Adverse effect was more frequent in theophylline treated children [47.4%] than in salbutamol group [24.4%]. Salbutamol is better tolerated than theophylline whereas both the drugs were equally effective for bronchodilation in infancy
Subject(s)
Humans , Male , Female , Respiratory Sounds/drug therapy , Albuterol , Theophylline , InfantABSTRACT
A list of 88 Plants belonging to 44 families dispensed by the local Hakims for the control of diabetes has been surveyed