Guinea pig histamine H1 receptor. II. Stable expression in Chinese hamster ovary cells reveals the interaction with three major signal transduction pathways.
A cDNA encoding a guinea pig histamine H1 receptor was stably expressed in Chinese hamster ovary (CHO) cells. In one resulting clone, named CHO(H1), the H1 receptor was found to be coupled to several major signal transduction pathways. In each case the involvement of a Gi/Go protein with pertussis toxin (PTX) was assessed, as well as the influence of extracellular Ca2+ and of protein kinase C activation by phorbol 12-myristate 13-acetate (PMA). Histamine induced, in a PTX- and PMA-insensitive manner, a biphasic increase in the intracellular Ca2+ level of which only the second sustained phase was dependent on the extracellular Ca2+ level. Histamine also caused a threefold elevation of inositol phosphate production, which was PTX-insensitive, but slightly inhibited by PMA and reduced by 75% in the absence of extracellular Ca2+. Histamine also caused a massive release of arachidonic acid, which occurred in a Ca(2+)- and PMA-sensitive manner, probably through the activation of a cytosolic phospholipase A2, which partly involves coupling to a PTX-sensitive G protein. In comparison, in HeLa cells endowed with a native H1 receptor, the histamine-induced arachidonic acid release was also Ca(2+)- and PMA-sensitive, but totally PTX-insensitive. Finally, in CHO(H1) cells, histamine in very low concentrations potentiated the cyclic AMP accumulation induced by forskolin. This response appeared to be insensitive to PTX, extracellular Ca2+, and PMA.(ABSTRACT TRUNCATED AT 250 WORDS)
Leurs
R
R
Unité de Neurobiologie et Pharmacologie, U. 109, INSERM, Centre Paul Broca, Paris, France.
Traiffort
E
E
Arrang
J M
JM
Tardivel-Lacombe
J
J
Ruat
M
M
Schwartz
J C
JC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D016466:CHO Cells / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D006168:Guinea Pigs; D006367:HeLa Cells; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D010716:Phosphatidylinositols / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D015398:Signal Transduction
D010716:Phosphatidylinositols; D011969:Receptors, Histamine H1; D005576:Colforsin; D016718:Arachidonic Acid; D006632:Histamine; D000242:Cyclic AMP; D002118:Calcium