RESUMEN
The cDNA encoding histamine H4 receptor was cloned from the porcine spleen cDNA library. Porcine H4 receptor, which shares 72% homology with its human counterpart, bound to histamine in receptor-expressing mammalian cells. Isolation of the porcine H4 receptor, which is important for understanding of the pharmacology, will aid in better interpretation of physiological role of this subtype of histamine receptor.
Asunto(s)
Receptores Acoplados a Proteínas G , Receptores Histamínicos/genética , Secuencia de Aminoácidos , Animales , Células CHO , Clonación Molecular , Cricetinae , ADN Complementario/genética , Datos de Secuencia Molecular , Especificidad de Órganos , Receptores Histamínicos/metabolismo , Alineación de Secuencia , PorcinosRESUMEN
Recent studies have identified two novel biofunctional proteins, termed prokineticin 1/EG-VEGF and prokineticin 2, which were mammalian homologues of mamba MIT1 and frog Bv8. Prokineticins have been demonstrated to exert their physiological functions through G-protein coupled receptors (GPCRs). In this study, we report the molecular identification of two endogenous prokineticin receptors, designated PK-R1 and PK-R2, through a search of the human genomic DNA database. PK-R1, locating in chromosome 2, and PK-R2, locating in chromosome 20p13, shared 87% homology, which was an extremely high value among known GPCRs. In functional assays, mammalian cells expressing PK-Rs responded to prokineticins in a concentration-dependent manner. Tissue distribution analysis revealed that expression of PK-R1 was observed in the testis, medulla oblongata, skeletal muscle and skin, while that of PK-R2 showed preferential expression in the central nervous system. The tissue distribution of PK-Rs reported in this paper suggests that the prokineticins play multifunctional roles in vivo.
Asunto(s)
Neuropéptidos , Receptores de Superficie Celular/genética , Receptores Acoplados a Proteínas G , Receptores de Péptidos/genética , Secuencia de Aminoácidos , Encéfalo/metabolismo , Clonación Molecular , ADN Complementario/biosíntesis , ADN Complementario/química , Hormonas Gastrointestinales/biosíntesis , Hormonas Gastrointestinales/metabolismo , Genes Reporteros , Humanos , Luciferasas/genética , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Receptores de Superficie Celular/química , Receptores de Superficie Celular/metabolismo , Receptores de Péptidos/química , Receptores de Péptidos/metabolismo , Testículo/metabolismoRESUMEN
Histamine H(4) receptor is considered as a novel therapeutic target for allergic diseases. To enhance the knowledge about species difference, which is essential for drug discovery research, monkey H(4) receptor was identified. Monkey H(4) receptor was characterized to have comparable similarity with its human counterpart. Discovery of monkey H(4) receptor will contribute to a better interpretation of effective drug discovery.