5HT/sub 2/ receptors coupled to phospholipase C in rat aorta are modulated by phorbol esters

Conference · Fri Feb 28 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5430633

Roth, B L; Nakaki, T; Costa, E; Chuang, D M

The authors previously demonstrated that 5HT recognition sites in rat aorta are coupled to a phosphoinositide (PI)-specific phospholipase C. Further, they showed that the mechanism of contraction elicited by 5HT is a complicated scenario involving receptor-mediated activation of calcium channels and a phospholipase C. They now report that in rat aorta, the 5HT-induced contraction and PI turnover are modulated by biologically active phorbol esters. In rat aorta the 5HT-induced contraction and PI hydrolysis (EC/sub 50/ = 10 +/- 3 ..mu..M) were highly correlated (r = 0.95; p < 0.01). Also, the inhibitory potency of a variety of 5HT/sub 2/ antagonists was correlated with binding to the brain 5HT/sub 2/ receptor (r = 0.90; p < 0.05). Further, the tumor-promoting phorbol ester, phorbol dibutyrate (PDB) inhibited 5HT-induced PI turnover at low nM concentrations (IC/sub 50/ approx. = to 30 nM), while the biologically inactive substance 4-..cap alpha..-phorbol was ineffective. Pretreatment of rat aortic rings with PDB at concentrations which desensitized 5HT-induced PI turnover also attenuated the aortic contraction induced by 5HT in the presence of a calcium channel blocker nitrendipine. Tge results suggest that phorbol esters desensitize 5HT receptor-mediated PI turnover and contraction, probably by activation of protein kinase C.

• Research Organization: Naval Medical Research Institute, Bethesda, MD
• OSTI ID: 5430633
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism &amp; Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
AORTA
AROMATICS
ARTERIES
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BLOOD VESSELS
BODY
CARBOHYDRATES
CARBOXYLESTERASES
CARCINOGENS
CARDIOVASCULAR SYSTEM
CHEMICAL REACTIONS
DECOMPOSITION
DRUGS
ENZYMES
ESTERASES
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROLYSIS
HYDROXY COMPOUNDS
INDOLES
INOSITOLS
KINETICS
LIPASE
LYSIS
MAMMALS
MEMBRANE PROTEINS
MONOSACCHARIDES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PHORBOL ESTERS
PHOSPHATES
PHOSPHORUS COMPOUNDS
PROTEINS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SACCHARIDES
SEROTONIN
SOLVOLYSIS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES