TRPV1-mediated calcium signal couples with cannabinoid receptors and sodium-calcium exchangers in rat odontoblasts

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• 作者：Maki Tsumura ; Ubaidus Sobhan ; Takashi Muramatsu ; Masaki Sato ; Hideki Ichikawa ; Yoshinori Sahara ; Masakazu Tazaki ; Yoshiyuki Shibukawa
• 关键词：2-AG ; 2-arachidonylglycerol ; AEA ; anandamide ; ANOVA ; analysis of variance ; cAMP ; cyclic adenosine monophosphate ; CAP ; capsaicin ; CB ; cannabinoid ; CPZ ; capsazepine ; DMP-1 ; dentin matrix protein-1 ; DSP ; dentin sialoprotein ; F ; RF340/F380 value ; F0 ; resting
• 刊名：Cell Calcium
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：52
• 期：2
• 页码：124-136
• 全文大小：2305 K

文摘

Odontoblasts are involved in the transduction of stimuli applied to exposed dentin. Although expression of thermo/mechano/osmo-sensitive transient receptor potential (TRP) channels has been demonstrated, the properties of TRP vanilloid 1 (TRPV1)-mediated signaling remain to be clarified. We investigated physiological and pharmacological properties of TRPV1 and its functional coupling with cannabinoid (CB) receptors and Na⁺-Ca²⁺ exchangers (NCXs) in odontoblasts. Anandamide (AEA), capsaicin (CAP), resiniferatoxin (RF) or low-pH evoked Ca²⁺ influx. This influx was inhibited by capsazepine (CPZ). Delay in time-to-activation of TRPV1 channels was observed between application of AEA or CAP and increase in [Ca²⁺]_i. In the absence of extracellular Ca²⁺, however, an immediate increase in [Ca²⁺]_i was observed on administration of extracellular Ca²⁺, followed by activation of TRPV1 channels. Intracellular application of CAP elicited inward current via opening of TRPV1 channels faster than extracellular application. With extracellular RF application, no time delay was observed in either increase in [Ca²⁺]_i or inward current, indicating that agonist binding sites are located on both extra- and intracellular domains. KB-R7943, an NCX inhibitor, yielded an increase in the decay time constant during TRPV1-mediated Ca²⁺ entry. Increase in [Ca²⁺]_i by CB receptor agonist, 2-arachidonylglycerol, was inhibited by CB1 receptor antagonist or CPZ, as well as by adenylyl cyclase inhibitor. These results showed that TRPV1-mediated Ca²⁺ entry functionally couples with CB1 receptor activation via cAMP signaling. Increased [Ca²⁺]_i by TRPV1 activation was extruded by NCXs. Taken together, this suggests that cAMP-mediated CB1-TRPV1 crosstalk and TRPV1-NCX coupling play an important role in driving cellular functions following transduction of external stimuli to odontoblasts.