The cAMP pathway sensitizes VR1 expressed in oocytes from Xenopus laevis and in CHO cells.
The vanilloid receptor 1 (VR1) is a heat-activated cation channel which also responds to capsaicin and other chemical stimuli. Protein kinase C has a stimulatory effect on VR1 activity, either alone or after activation with capsaicin. The influence of the cAMP-signaling pathway on the effects of capsaicin is controversial. To clarify this, the actions of capsaicin and the modulatory effects of forskolin, pCPT-cAMP, and isobutylmethylxanthine were studied in Xenopus laevis oocytes expressing rat VR1 and in CHO cells expressing human VR1. Capsaicin activated the VR1 channel and increased the intracellular calcium concentration. The effects of capsaicin were enhanced by forskolin, pCPT-cAMP, and isobutylmethylxanthine. A modulatory function of the cAMP system on VR1 activation could, therefore, modulate heat sensation and pain.
Vulcu
Sebastian D
SD
Department of Pharmacology, University of Mainz, Mainz, Germany.
Rupp
Johanna
J
Wiwie
Caroline
C
Gillen
Clemens
C
Jostock
Ruth
R
Nawrath
Hermann
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002211:Capsaicin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004789:Enzyme Activation; D007473:Ion Channels; D009865:Oocytes / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D050916:TRPV Cation Channels; D013873:Thionucleotides / Q000494:pharmacology; D014982:Xenopus laevis
D007473:Ion Channels; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D013873:Thionucleotides; C476722:Trpv2 protein, rat; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D011493:Protein Kinase C; D002211:Capsaicin; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine