Substance P enhances forskolin-stimulated cyclic AMP production in human UC11MG astrocytoma cells.
The effects of substance P (SP) upon basal and forskolin-stimulated cAMP production have been investigated in UC11MG cells. The cells expressed 40,000 NK1 receptors/cell, the stimulation of which led to enhanced phosphoinositide breakdown. Forskolin (10 and 100 mcM) stimulated cAMP production, whereas SP (3 and 300 nM) produced no significant increase in cAMP production. However, SP enhanced the response to forskolin, with an EC50 value of about 10 nM. The response to forskolin was also enhanced by physalaemin and eledoisin, and was sensitive to inhibition by (+/-)CP96345. It is concluded that in the UC11MG cell line, SP not only stimulates phosphoinositide breakdown but also enhances the cAMP response to forskolin, possibly via stimulation of NK1 receptors.
Fowler
C J
CJ
Department of Biochemical Pharmacology, Astra Pain Control AB, Preclinical R&D, Huddinge, Sweden.
Brännström
G
G
D000262:Adenylyl Cyclases / Q000378:metabolism; D001254:Astrocytoma / Q000201:enzymology / Q000378:metabolism*; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004347:Drug Interactions; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism; D010803:Physalaemin / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism*
D010716:Phosphatidylinositols; C062618:substance P, Sar(9)-Met(O2)(11)-; D005576:Colforsin; D010803:Physalaemin; D013373:Substance P; D000242:Cyclic AMP; D000262:Adenylyl Cyclases