Enhancement of adenylate cyclase stimulation by prostaglandin E receptor EP3 subtype isoforms with different efficiencies.
We recently cloned the mouse prostaglandin (PG) E receptor EP3 subtype that is coupled to adenylate cyclase inhibition through Gi and identified two isoforms of EP3, EP3 alpha and EP3 beta, which are produced through alternative splicing and differ only in the carboxyl-terminal domain. Preincubation of Chinese hamster ovary cells expressing each isoform with PGE2 concentration-dependently enhanced both the basal and forskolin-stimulated cAMP formation, but two orders higher concentrations of PGE2 were required for EP3 beta than EP3 alpha for 50% enhancement of both formations. This enhancement by EP3 isoforms was completely blocked by pertussis toxin treatment, indicating that it is mediated through Gi activation. Thus, the two EP3 isoforms with different carboxyl-terminal tails induce enhancement of adenylate cyclase stimulation with different efficiencies.
Harazono
A
A
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Sugimoto
Y
Y
Ichikawa
A
A
Negishi
M
M
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004789:Enzyme Activation; D051379:Mice; D037342:Pertussis Toxin; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D018078:Receptors, Prostaglandin E; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D015232:Dinoprostone