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J Klomp

Publications and source records attributed to J Klomp.

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Molecular cloning and characterization of a novel orphan receptor (P2P) expressed in human pancreas that shows high structural homology to the P2U purinoceptor.

Here we report the cloning of a gene encoding a new member of the superfamily of G protein-coupled receptors. The gene encodes a protein of 365 amino acids closely resembling two recently cloned nucleotide binding receptors, called P2U and P2Y purinoceptors (71% and 49% sequence identity within the transmembrane domains, respectively). Our studies show that this new putative purinoceptor (designated P2P) is encoded by an intronless single copy gene that is exclusively expressed in pancreas, in contrast to the P2U and the P2Y purinoceptors which are widely distributed throughout the periphery. The identification of a pancreas-specific human putative P2 purinoceptor makes it attractive to speculate that the reported actions of ADP/ATP analogues in pancreas on insulin secretion are mediated through this receptor.

Amino Acid Sequence

Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor.

The 5-HT2C receptor gene is unique among the members of the 5-HT receptor family by virtue of its genomic organisation. The human 5-HT2C receptor gene, unlike many other genes for guanine nucleotide binding (G)-proteins, contains three introns which interrupt the coding sequence into four exons. The first two introns are at equivalent positions as compared to the intervening sequences previously found in the 5-HT2(A) receptor gene, suggesting a close evolutionary relationship between both genes. Southern blot analysis shows that the 5-HT2C receptor gene is a single copy gene. Furthermore, we report the functional expression of a complementary DNA for the 5-HT2C receptor, cloned from hippocampal RNA. Membranes prepared from NIH 3T3 cells stably expressing the 5-HT2C receptor cDNA, displayed a single population of high affinity sites for the antagonist [3H]mesulergine (Kd = 2.9 +/- 0.4 nM, Bmax = 44.3 +/- 7.2 pmol/mg protein) as well as for [3H]5-HT (Kd = 9.9 +/- 0.7 nM, Bmax = 13.6 +/- 1.0 pmol/mg protein). Displacement of [3H]mesulergine and [3H]5HT binding by ligands indicated a pharmacological similarity of these binding sites with porcine and rat choroid plexus 5-HT2C receptors. Furthermore, activation of the 5-HT2C receptor with 5-HT results in an increased phospholipase C activity.

3T3 Cells

[Hydramnics].

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