Figure 1
From: Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins
Physiological interaction of PGE2 with TRPV1 in mice. (A) PGE2-induced thermal hyperalgesia in TRPV1+/+ mice (○, n = 6) or TRPV1-/- mice (▲, n = 6). Reduction of paw withdrawal latency (thermal hyperalgesia) by intraplantar PGE2 (500 pmol/ 20 μL) injection was significantly diminished in TRPV1-/- mice. * p < 0.05, ** p < 0.01 vs. TRPV1+/+ mice. (B) Intracellular cAMP levels in mouse DRG neurons or HEK293 cells treated with a mixture of forskolin (FSK, 10 μM), IBMX (1 mM) and dibutyryl cAMP (dbcAMP, 3 mM), or PGE2 (1 μM) or isoproterenol (Isop., 10 μM). *, # p < 0.05 vs. Cont., **, ## p < 0.01 vs. Cont. (C) Representative traces of potentiation of capsaicin (100 nM)-activated current by extracellular PGE2 (1 μM, 1.5 min) or a mixture of FSK(10 μM), IBMX (1 mM) and dbcAMP (3 mM) (6.5 min) in mouse DRG neurons. Currents were normalized to values induced by first capsaicin application in the absence of additives (bar graph). Capsaicin was reapplied 1.5 or 6.5 min after exposure to bath solution with additives. Numbers in parenthesis indicate cells tested. * p < 0.05 vs. Cont. Holding potential (Vh): -60 mV. (D) Long (6.5 min) but not short (1.5 min) activation of PKA pathway has effect on TRPV1 responses in HEK293 cells. FSK (10 μM), IBMX (1 mM) and dbcAMP (3 mM) were applied to cells expressing rat TRPV1. Isop. (10 μM) was applied to cells expressing both rat TRPV1 and β1-adrenergic receptors (β1-ADR). Numbers in parenthesis indicate cells tested. Vh: -60 mV. * p < 0.05 vs Cont.