The autacoid and neurotransmitter histamine activates the H 1 G protein-coupled receptor (GPCR) to stimulate predominantly phospholipase C (PLC)/inositol phosphate (IP) signaling and, to a lesser extent, adenylyl cyclase (AC)/cAMP signaling in a variety of mammalian cells and tissues, as well as H 1 -transfected clonal cell lines. This study reports that two novel H 1 receptor ligands developed in our laboratory, (Ϫ)-trans-1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (trans-PAT) and (Ϯ)-cis- 5-phenyl-7-dimethylamino-5,6,7,8-tetrahydro-9H- Results suggest the trans-PAT and cis-PAB probes will be useful to study molecular mechanisms of liganddirected GPCR multifunctional signaling. Moreover, because most untoward cardiovascular-, respiratory-, and gastrointestinal H 1 receptor-mediated effects proceed via the PLC/IP pathway, PAT-type agonists that selectively enhance H 1 -mediated AC/cAMP signaling provide a mechanistic basis for exploiting H 1 receptor activation for drug design purposes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.