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

The effects of 10(-5) M trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamidel (U-50488H), a kappa-opioid receptor agonist, on cytosolic Ca2+ concentration ([Ca2+]i) and the [Ca2+]i transient in quiescent and electrically stimulated rat ventricular myocytes, respectively, were determined after the cells had been pretreated with pertussis toxin (PTX) or a tyrosine kinase inhibitor (genistein or tyrphostin). The [Ca2+]i was determined with a spectrofluorometric method, with fura 2 as Ca2+ indicator. U-50488H at 10(-5) M itself induced a [Ca2+]i transient in the quiescent cells but inhibited the [Ca2+]i transient in electrically stimulated cells. The effects of 10(-5) M U-50488H on [Ca2+]i, which were blocked by a selective kappa-opioid receptor antagonist, nor-binaltorphimine (10(-6) M), were abolished after pretreatment with PTX (1 microg/ml) for 24 h, but not with genistein (10(-4) M) or tyrphostin (5 x 10(-5) M) for 30 min. 1-[6-[[(17b)-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexy l]-1H-pyrrole-2,5-dione (U-73122), an inhibitor of phospholipase C, at 10(-5) M, but not its inactive structural isomer 1-[6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexy l]-2,5-pyrrolidinedione (U-73343), also blocked the Ca2+ responses to U-50488H. The results indicate that activation of phospholipase C on kappa-opioid receptor stimulation is via PTX-sensitive G proteins but does not involve protein tyrosine phosphorylation.
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PMID:Pertussis toxin, but not tyrosine kinase inhibitors, abolishes effects of U-50488H on [Ca2+]i in myocytes. 912 99

Intracellular recording methods with "sharp" microelectrodes were used to study signal transduction mechanisms underlying the excitatory action of bradykinin (BK) in morphologically identified neurons in the small intestinal submucosal plexus. Exposure to BK evoked slowly activating membrane depolarization and enhanced excitability associated with increased input resistance in AH-type and decreased input resistance in S-type neurons. Preincubation with pertussis toxin did not affect the BK-evoked responses. Pretreatment with the cyclooxygenase inhibitors indomethacin or piroxicam suppressed or abolished the BK-evoked responses. Application of prostaglandin (PG) E(2) or PG analogs evoked BK-like depolarizing responses in the submucosal plexus with a potency order of PGE(2) > PGE(1) > 17-phenyl trinor-PGE(2) > PGI(2) > sulprostone > PGF(2alpha). Depolarizing responses to bradykinin or PGE(2) in S-type neurons were suppressed in the presence of the phospholipase C inhibitor U73122 [(1-6-[([17beta]-3-methoxyestra-1,3,5[10]-tren-17-71)amino]hexyl)-1H-pyrrole-2,5-dione)], but not the inactive analog U73343 [(1-6-[([17beta]-3-methoxyestra-1,3,5[10]trien-17yl)amino]hexyl)-2,5-pyrrolidinedione)]. The inositol-1,4,5-trisphosphate receptor antagonist 2-aminoethoxy-diphenylborane and the calmodulin inhibitor W-7, but not ryanodine, suppressed both bradykinin- and PGE(2)-evoked responses. KN-62, an inhibitor of calmodulin kinases, or GF109203X, a specific protein kinase C inhibitor, suppressed both BK- and PGE(2)-evoked depolarizing responses. Selective protein kinase A inhibitors did not alter BK- or PGE(2)-evoked depolarizing responses in S neurons. The results suggest that BK stimulates synthesis and release of PGE(2), which acts at EP(1) receptors to evoke depolarizing responses in submucosal neurons. The postreceptor transduction cascade includes activation of phospholipase C, inositol-1,4,5-trisphosphate production, intraneuronal Ca2+ mobilization, activation of protein kinase C and/or calmodulin kinases, and phosphorylation of cationic channels.
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PMID:Metabotropic signal transduction for bradykinin in submucosal neurons of guinea pig small intestine. 1471 1