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We have observed the decays B° -» K*(892)°j and B~ -> K*(892)~ry, which are evidence for the quark-level process b -• 57. The average branching fraction is (4.5 ± 1.5 ± 0.9) x 10~5. This value is consistent with standard model predictions from electromagnetic penguin diagrams. PACS numbers: 13.40.Hq, 14.40.Jz One-loop, flavor-changing neutral current diagrams, meson decays [1]. They were later identified as a possible known as penguins, were originally introduced into the source of direct CP violation in kaon decay, and hence as theory of weak decays to explain the AI = \ rule in K a contribution to e! /e [2]. Their importance in B meson 674 0031 -9007/93/71 (5)/674(5)$06.00

The 5-hydroxytryptamine 5-HT 1A receptor was one of the ®rst G protein coupled receptors whose cDNA and gene were isolated by molecular cloning methods. Transfection of the cDNA of this receptor into cells previously bearing no 5-HT receptors has resulted in the acquisition of large amounts of information regarding potential signal transduction pathways linked to the receptor, correlations of receptor structure to its various functions, and pharmacological properties of the receptor. Transfection studies with the 5-HT 1A receptor have generated critical new information that might otherwise have been elusive. This information notably includes the discovery of unsuspected novel signalling linkages, the elucidation of the mechanisms of receptor desensitization, the re®nement of models of the receptor pharmacophore, and the development of silent receptor antagonists, among others. The current review summarizes the most important studies of the recombinant 5-HT 1A receptor in the decade since the identi®ciation of its cDNA. Keywords: 5-Hydroxytryptamine; transfection; G protein; adenylyl cyclase; phospholipase; calcium; ecacy; potency Abbreviations: cyclic AMP, 3',5'-cyclic adenosine monophosphate; CFTR, cystic ®brosis transmembrane regulator; DAG, diacylglycerol; Erk, extracellular signal-regulated kinase; G protein, guanine nucleotide regulatory binding protein; G i , G protein that inhibits adenylyl cyclase; GIRK, G protein-gated inwardly recti®ed K + channel; G o , G protein that serves functions other than to regulate adenylyl cyclase; G q , G protein that activates phospholipase C; Grb2, protein that serves as a molecular adapter; GRK, G protein-coupled receptor kinase; GTP, guanosine triphosphate; GTPgS, nonhydrolysable GTP analogue; G S , G protein that stimulates adenylyl cyclase; 8-OH-DPAT, 8-hydroxy-2-(di-n-propylamino)-tetralin; 5-HT, 5-hydroxytryptamine; serotonin; i2 loop, putative second intracellular loop of the 5-HT 1A receptor protein; i3 loop, putative third intracellular loop of the 5-HT 1A receptor protein; IkBa, inhibitor of NF-kB; IP 3 , inositol triphosphate; Mek, mitogen and extracellular signal regulated kinase, which phosphorylates and activates Erk; NF-kB, nuclear factor-kB; PC-PLC, phosphatidylcholine-speci®c phospholipase C; PI-PLC, phosphatidylinositol-speci®c phospholipase C; PKA, cyclic AMP-dependent protein kinase; PKC, protein kinase C; PLA 2 , phospholipase A 2 ; PLC, phospholipase C; Raf; a kinase that is activated by Ras, and that phosphorylates and activates MEK; Ras, a monomeric low molecular weight G protein that activates Raf; RGS proteins, regulators of G protein signalling; ROI, reactive oxygen intermediates; R-SAT, receptor selection and ampli®cation technology; Shc, a protein that serves as a docking platform; Src, non-receptor tyrosine kinase; WAY-100635, N-[2-[4-(2-methoxyphenyl)1-piperazinyl]ethyl)-n-(2-pyridiynl)cyclohexanecarboxamide trihydrochloride

Lysophosphatidic acid (LPA) is a lipid mediator that may play an important role in growth and survival of carcinomas. In this study, LPA production and response were characterized in two human prostate cancer (CaP) cell lines: PC-3 and Du145. Bombesin, a neuroendocrine peptide that is mitogenic for CaP cells, stimulated focal adhesion kinase phosphorylation and activated the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. Similar responses were elicited by 18:1 LPA (oleoyl-LPA). Studies using radioisotopic labeling revealed that both PC-3 and Du145 generate LPA and that LPA production is increased by bombesin. The kinetics of bombesin-induced phospholipase D activation and LPA production were similar. Using electrospray ionization mass spectrometry, 18:1 LPA was found to be an abundant LPA species in CaP cell medium. Structure activity studies of acyl-LPAs revealed that 18:1 LPA is most efficacious for activation of extracellular signal-regulated kinase and phospholipase D in CaP cells. Incubation with 18:1 LPA caused homologous desensitization of LPA response, whereas bombesin caused heterologous desensitization. LPA was present at nanomolar levels in medium from bombesin-treated cells. LPA extracted from the medium induced calcium mobilization in CaP cells. These results demonstrate that bioactive LPA is generated by CaP cells in response to a mitogen and suggest that 18:1 LPA can act as an autocrine mediator.