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)

In the present study, we have identified the expression of adenylyl cyclase (AC) isoforms in rat neutrophils according to the mRNA analysis and the distinct mode of regulation of isoform activity. Agarose gel electrophoresis of reverse transcription-polymerase chain reaction (RT-PCR)-amplified products resulted in a single band of the expected size for each product with nucleotide sequences corresponding to AC1 to AC9. AC1 was abundant, while AC2, 6 and 9 were of moderate expression among the AC isoforms in neutrophils based on the quantitative real-time RT-PCR analysis. Exposure of neutrophils to Ca(2+) ionophore A23187, isoproterenol and forskolin stimulated cellular cyclic AMP accumulation. EDTA and the calmodulin (CaM) antagonist, trifluoperazine, prevented the A23187-induced response. Pretreatment with pertussis toxin (PTX) inhibited the alpha(2)-adrenergic agonist, UK14304-induced cellular cyclic AMP elevation. In addition, UK14304 augmented the cyclic AMP elevation when cells were stimulated by isoproterenol. Phorbol 12-myristate 13-acetate (PMA) attenuated the augmentation response of UK14304 and isoproterenol. Treatment of the membrane preparations from rat neutrophils with Ca(2+)/CaM, forskolin, isoproterenol, GTPgammaS or Gbetagamma all increased cyclic AMP production. The addition of protein kinase C (PKC) catalytic fragment and Gbetagamma augmented the Ca(2+)/CaM- and isoproterenol-stimulated AC activity, respectively. However, forskolin and the activated protein kinase A (PKA) attenuated the GTPgammaS- and isoproterenol-stimulated AC activity, respectively. KT5720, a PKA inhibitor, reversed the inhibition by PKA. Taken together, these data suggest the presence of four groups of AC isoforms in rat neutrophils.
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PMID:Expression of adenylyl cyclase isoforms in neutrophils. 1267 54

Nine membrane-bound members of the mammalian adenylate cyclase family have been identified. The least characterized and most divergent in sequence of the nine adenylate cyclase isoforms is AC9. Stimulation by Galpha(s) and inhibition by Ca2+/calcineurin are two modes of regulation that have been reported for AC9. We explored the possibility of additional modes of regulation of human AC9. We now report that quinpirole activation of the inhibitory G protein-coupled D2L dopamine receptor inhibits Galpha(s) stimulation of AC9 by approximately 50%. The effects of quinpirole were reversed by the D2 antagonist spiperone and by pertussis toxin pretreatment. We also report the first evidence for regulation of AC9 by protein kinase C (PKC). Specifically, phorbol ester activation of PKC significantly attenuated (approximately 50%) Galpha(s)-stimulated AC9 activity. The effect of PKC activation on AC9 was reversed by the PKC inhibitor bisindolylmaleimide. Galpha(s)-stimulated cyclic accumulation was reduced more by simultaneous addition of both quinpirole and phorbol 12-myristate 13-acetate than by either drug alone. Additional studies investigated the role of glycosylation on AC9 activity. The results show that blocking glycosylation of AC9 significantly attenuates Galpha(s) stimulation. In contrast, the ability of PKC and Galpha(i/o) to negatively regulate AC9 did not seem to be affected by the glycosylation state of AC9. These observations demonstrate the diverse regulatory features of AC9 and the ability of AC9 to integrate multiple signals.
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PMID:Novel regulatory properties of human type 9 adenylate cyclase. 1499 50