Potentiation of cyclic AMP-mediated proopiomelanocortin gene promoter activity by calcium channel blockers in a pituitary cell line.

Abstract

Although it is known that the expression of proopiomelanocortin, a precursor protein of adrenocorticotropic hormone, can be affected by a variety of drugs, the effects of calcium channel blockers have not been studied. This study examined the effect of calcium channel blockers on proopiomelanocortin gene expression. Mouse pituitary tumor cells stably transfected with approximately 0.7 kb of the rat proopiomelanocortin 5' promoter-luciferase fusion gene were stimulated by potassium chloride, corticotropin-releasing hormone (CRH) or forskolin, in the presence or absence of calcium channel blockers (nifedipine, verapamil and diltiazem). Assessments were made of proopiomelanocortin gene promoter activity and cyclic adenosine 3',5'-monophosphate (cyclic AMP) efflux. A dose-dependent enhancement of CRH- or forskolin-stimulated proopiomelanocortin promoter activity was observed with nifedipine and verapamil, but not diltiazem. Cyclic AMP efflux induced by CRH or forskolin was also enhanced by nifedipine and verapamil. In the presence of isobutylmethylxanthine, a phosphodiesterase inhibitor, enhancement of proopiomelanocortin promoter activity and cyclic AMP efflux by nifedipine and verapamil was not observed. It was concluded that the inhibition of phosphodiesterase is a probable mechanism for the effect of nifedipine and verapamil on CRH or forskolin induction of proopiomelanocortin gene expression.

• Authors: Masahiro Ikeda, Masahiro Kakuyama, Takehiro Shoda, Yasumasa Iwasaki, Kazuhiko Fukuda
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 558 Issue 1-3 Pg. 1-6 (Mar 08 2007) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17196958 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Colforsin
• Pro-Opiomelanocortin
• Adrenocorticotropic Hormone
• Corticotropin-Releasing Hormone
• Cyclic AMP

Topics

• Adrenocorticotropic Hormone (biosynthesis)
• Animals
• Calcium Channel Blockers (pharmacology)
• Cell Line
• Colforsin (pharmacology)
• Corticotropin-Releasing Hormone (pharmacology)
• Cyclic AMP (physiology)
• Mice
• Pituitary Gland (metabolism)
• Pro-Opiomelanocortin (genetics)
• Promoter Regions, Genetic