PMID- 22656960 OWN - NLM STAT- MEDLINE DCOM- 20121030 LR - 20161125 IS - 1532-1991 (Electronic) IS - 0143-4160 (Linking) VI - 52 IP - 2 DP - 2012 Aug TI - TRPV1-mediated calcium signal couples with cannabinoid receptors and sodium-calcium exchangers in rat odontoblasts. PG - 124-36 LID - 10.1016/j.ceca.2012.05.002 [doi] AB - 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(+)-Ca(2+) exchangers (NCXs) in odontoblasts. Anandamide (AEA), capsaicin (CAP), resiniferatoxin (RF) or low-pH evoked Ca(2+) 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 [Ca(2+)](i). In the absence of extracellular Ca(2+), however, an immediate increase in [Ca(2+)](i) was observed on administration of extracellular Ca(2+), 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 [Ca(2+)](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 Ca(2+) entry. Increase in [Ca(2+)](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 Ca(2+) entry functionally couples with CB1 receptor activation via cAMP signaling. Increased [Ca(2+)](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. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Tsumura, Maki AU - Tsumura M AD - Oral Health Science Center hrc8, Tokyo Dental College, Chiba, Japan. FAU - Sobhan, Ubaidus AU - Sobhan U FAU - Muramatsu, Takashi AU - Muramatsu T FAU - Sato, Masaki AU - Sato M FAU - Ichikawa, Hideki AU - Ichikawa H FAU - Sahara, Yoshinori AU - Sahara Y FAU - Tazaki, Masakazu AU - Tazaki M FAU - Shibukawa, Yoshiyuki AU - Shibukawa Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120530 PL - Netherlands TA - Cell Calcium JT - Cell calcium JID - 8006226 RN - 0 (2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate) RN - 0 (Arachidonic Acids) RN - 0 (Calcium Channel Agonists) RN - 0 (Calcium Channel Blockers) RN - 0 (Cannabinoid Receptor Antagonists) RN - 0 (Diterpenes) RN - 0 (Endocannabinoids) RN - 0 (Glycerides) RN - 0 (Polyunsaturated Alkamides) RN - 0 (Receptors, Cannabinoid) RN - 0 (Sodium-Calcium Exchanger) RN - 0 (TRPV Cation Channels) RN - 0 (Trpv1 protein, rat) RN - 8D239QDW64 (glyceryl 2-arachidonate) RN - A5O6P1UL4I (resiniferatoxin) RN - E0399OZS9N (Cyclic AMP) RN - GYV9AM2QAG (Thiourea) RN - LFW48MY844 (capsazepine) RN - S07O44R1ZM (Capsaicin) RN - SY7Q814VUP (Calcium) RN - UR5G69TJKH (anandamide) SB - IM MH - Animals MH - Arachidonic Acids/pharmacology MH - Calcium/metabolism MH - Calcium Channel Agonists/pharmacology MH - Calcium Channel Blockers/pharmacology MH - Calcium Signaling/drug effects MH - Cannabinoid Receptor Antagonists MH - Capsaicin/analogs & derivatives/pharmacology MH - Cyclic AMP/metabolism MH - Diterpenes/pharmacology MH - Endocannabinoids MH - Glycerides/pharmacology MH - Hydrogen-Ion Concentration MH - Odontoblasts/cytology/drug effects/*metabolism MH - Polyunsaturated Alkamides/pharmacology MH - Rats MH - Rats, Wistar MH - Receptors, Cannabinoid/*metabolism MH - Sodium-Calcium Exchanger/*metabolism MH - TRPV Cation Channels/agonists/antagonists & inhibitors/*metabolism MH - Thiourea/analogs & derivatives/pharmacology EDAT- 2012/06/05 06:00 MHDA- 2012/10/31 06:00 CRDT- 2012/06/05 06:00 PHST- 2011/12/30 00:00 [received] PHST- 2012/04/24 00:00 [revised] PHST- 2012/05/02 00:00 [accepted] PHST- 2012/06/05 06:00 [entrez] PHST- 2012/06/05 06:00 [pubmed] PHST- 2012/10/31 06:00 [medline] AID - S0143-4160(12)00089-9 [pii] AID - 10.1016/j.ceca.2012.05.002 [doi] PST - ppublish SO - Cell Calcium. 2012 Aug;52(2):124-36. doi: 10.1016/j.ceca.2012.05.002. Epub 2012 May 30.