Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of adenosine on inward current activated by extracellular ATP were examined in rat pheochromocytoma PC12 cells. Adenosine induced two types of modulation on the current activated by 30 microM ATP; a low concentration of adenosine (1 microM) inhibited the current whereas a high concentration (> 10 microM) enhanced the current. Neither the inhibition nor the enhancement was observed in cells pretreated with pertussis toxin (PTX), or in cells dialyzed with guanosine 5'-O-(2-thiotriphosphate) trilithium salt (GDP beta S). In contrast, dialysis with K-252a, a protein kinase inhibitor, abolished the inhibition, but not the enhancement. Adenosine induced similar inhibition and enhancement on ATP-evoked increase in intracellular free Ca2+ concentration. The results suggest that adenosine produces dual modulation on the ATP-activated channels through different mechanisms involving PTX-sensitive GTP-binding proteins.
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PMID:Dual modulation by adenosine of ATP-activated channels through GTP-binding proteins in rat pheochromocytoma PC12 cells. 752 18

1. Inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current was characterized in rat phaeochromocytoma PC12 cells by use of whole-cell voltage-clamp techniques. 2. Haloperidol or chlorpromazine (1 and 10 microM) inhibited a K+ current activated by a test potential of +20 mV applied from a holding potential of -60 mV. The K+ current inhibition did not exhibit voltage-dependence when test potentials were changed between -10 and +40 mV or when holding potentials were changed between -120 and -60 mV. 3. Effects of compounds that are related to haloperidol and chlorpromazine in their pharmacological actions were examined. Fluspirilene (1 and 10 microM), an antipsychotic drug, inhibited the K+ current, but pimozide (1 and 10 microM), another antipsychotic drug did not significantly inhibit the K+ current. Sulpiride (1 or 10 microM), an antagonist of dopamine D2 receptors, did not affect the K+ current whereas (+)-SCH-23390 (10 microM), an antagonist of dopamine D1 receptors, reduced the K+ current. As for calmodulin antagonists, W-7 (100 microM), but not calmidazolium (1 microM), reduced the K+ current. 4. The inhibition by haloperidol or chlorpromazine of the K+ current was abolished when GTP in intracellular solution was replaced with GDP beta S. Similarly, the inhibition by pimozide, fluspirilene, (+)-SCH-23390 or W-7 was abolished or attenuated in the presence of intracellular GDP beta S. The inhibition by haloperidol or chlorpromazine was not prevented when cells were pretreated with pertussis toxin or when K-252a, an inhibitor of a variety of protein kinases, was included in the intracellular solution. 5. Haloperidol and chlorpromazine reduced a Ba2+ current permeating through Ca2+ channels. Inhibition by haloperidol or chlorpromazine of the Ba2+ current was not affected by GDP beta S included in the intracellular solution. 6. It is concluded that haloperidol and chlorpromazine inhibit voltage-gated K+ channels in PC12 cells by a mechanism involving GTP-binding proteins. The inhibition may not be related to their activity as antagonists of dopamine D2 receptors or calmodulin antagonists.
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PMID:Characterization of inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current in rat phaeochromocytoma cells. 859 Sep 77