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)

Neurokinins are a family of neuropeptides with widespread distribution mediating a broad spectrum of physiological actions through three distinct receptor subtypes: NK-1, NK-2, and NK-3. We investigated some of the second messenger and cellular processes under control by the recombinant bovine NK-2 receptor stably expressed in Chinese hamster ovary cells. In this system the NK-2 receptor displays its expected pharmacological characteristics, and the physiological agonist neurokinin A stimulates several cellular responses. These include 1) transient inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization, 2) increased out put of arachidonic acid and prostaglandin E2 (PGE2), 3) enhanced cyclic AMP (cAMP) generation, 4) increased de novo DNA synthesis, and 5) an induction of the "immediate early" genes c-fos and c-jun. Although NK-2 receptor-mediated IP3 formation involves activation of a pertussis toxin-insensitive G-protein, increased cAMP production is largely a secondary response and can be at least partially attributed to autocrine stimulation by endogenously generated eicosanoids, particularly PGE2. This is the first demonstration that a single recombinant neurokinin receptor subtype can regulate, either directly or indirectly, multiple signal transduction pathways and suggests several potential important mediators of neurokinin actions under physiological conditions.
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PMID:Recombinant bovine neurokinin-2 receptor stably expressed in Chinese hamster ovary cells couples to multiple signal transduction pathways. 166 1

We identified clones encoding a Drosophila receptor for tachykinin-like peptides by low stringency screening of an embryonic cDNA library with probes from the bovine substance K receptor. The cDNAs encode a seven transmembrane domain protein (DTKR) of 519 amino acids with 40-48% amino acid identity to mammalian tachykinin receptors within transmembrane regions. Xenopus oocytes injected with DTKR cRNAs showed selective responses to vertebrate substance P, its agonists and not to other vertebrate tachykinin peptides. These responses were eliminated by treatment of oocytes with pertussis toxin. In the adult fly, Northern and PCR analysis demonstrated preferential expression of DTKR in the head; in situ hybridization indicated that DTKR is accumulated in the cell bodies of neurons in the adult CNS. The levels of DTKR transcript are regulated during development. Northern and PCR amplification analysis showed that while DTKR transcripts are present at all stages, high levels of expression occur in later stages of embryogenesis (starting at 10-14 h), coinciding with the beginning of major periods of neural development. Whole mount embryo in situ hybridization demonstrated that DTKR is expressed at these later stages of embryogenesis (11-15 h) in the brain and in a specific subset of neurons in each neuromere of the developing ventral ganglion. The gene encoding DTKR was mapped by in situ hybridization to a single location at 99D on the right arm of chromosome 3. These observations demonstrate that the tachykinin family of peptide transmitters and their receptors represent an evolutionarily ancient form of cellular communication within the nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cloning, heterologous expression and developmental regulation of a Drosophila receptor for tachykinin-like peptides. 171 63

C6-2B rat glioma cells were stably transfected with substance K receptor cDNA and used to study interactions between cAMP and Ca2+ signaling pathways. Activation of the newly expressed receptors by substance K increased the intracellular free Ca2+ concentration, as monitored by single-cell fura-2 imaging, and markedly inhibited agonist-stimulated cAMP accumulation. Blockade of intracellular Ca2+ mobilization abolished the substance K receptor-mediated inhibition of isoproterenol-induced cAMP production. Phosphodiesterase inhibitors, down-regulation or inhibition of protein kinase C, and pertussis toxin failed to prevent substance K-induced inhibition of agonist-stimulated cAMP accumulation. An increased intracellular Ca2+ concentration caused by either calcium ionophores or activation of endogenous bradykinin receptors was found to markedly reduce cAMP production in wild-type cells. These results demonstrate that elevated intracellular Ca2+ concentration can negatively modulate agonist-stimulated adenylate cyclase activity in C6-2B glioma cells.
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PMID:Inhibition of cAMP accumulation by intracellular calcium mobilization in C6-2B cells stably transfected with substance K receptor cDNA. 171 1