{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:38:08Z","timestamp":1791189488437,"version":"4.1.0"},"reference-count":41,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:p>\n                    The transient receptor potential melastatin 8 (TRPM8) channel has been characterized as a cold and menthol receptor expressed in a subpopulation of sensory neurons but was recently identified in other tissues, including the respiratory tract, urinary system, and vasculature. Thus TRPM8 may play multiple functional roles, likely to be in a tissue- and activation state-dependent manner. We examined the TRPM8 channel presence in large arteries from rats and the functional consequences of their activation. We also aimed to examine whether these channels contribute to control of conscious human skin blood flow. TRPM8 mRNA and protein were detected in rat tail, femoral and mesenteric arteries, and thoracic aorta. This was confirmed in single isolated vascular myocytes by immunocytochemistry. Isometric contraction studies on endothelium-denuded relaxed rat vessels found small contractions on application of the TRPM8-specific agonist menthol (300 \u03bcM). However, both menthol and another agonist icilin (50 \u03bcM) caused relaxation of vessels precontracted with KCl (60 mM) or the \u03b1-adrenoceptor agonist phenylephrine (2 \u03bcM) and a reduction in sympathetic nerve-mediated contraction. These effects were antagonized by bromoenol lactone treatment, suggesting the involvement of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -independent phospholipase A\n                    <jats:sub>2<\/jats:sub>\n                    activation in TRPM8-mediated vasodilatation. In thoracic aorta with intact endothelium, menthol-induced inhibition of KCl-induced contraction was enhanced. This was unaltered by preincubation with either N\n                    <jats:sup>\u03c9<\/jats:sup>\n                    -nitro-l-arginine methyl ester (l-NAME; 100 nM), a nitric oxide synthase inhibitor, or the ACh receptor antagonist atropine (1 \u03bcM). Application of menthol (3% solution, topical application) to skin caused increased blood flow in conscious humans, as measured by laser Doppler fluximetry. Vasodilatation was markedly reduced or abolished by prior application of l-NAME (passive application, 10 mM) or atropine (iontophoretic application, 100 nM, 30 s at 70 \u03bcA). We conclude that TRPM8 channels are present in rat artery vascular smooth muscle and on activation cause vasoconstriction or vasodilatation, dependent on previous vasomotor tone. TRPM8 channels may also contribute to human cutaneous vasculature control, likely with the involvement of additional neuronal mechanisms.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.01112.2008","type":"journal-article","created":{"date-parts":[[2009,4,10]],"date-time":"2009-04-10T20:44:50Z","timestamp":1239396290000},"page":"H1868-H1877","source":"Crossref","is-referenced-by-count":134,"title":["Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone"],"prefix":"10.1152","volume":"296","author":[{"given":"Christopher D.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donal","family":"Melanaphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Purse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Stokesberry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Zholos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605779200"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.096875"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Bautista DM\n                      , Siemens J, Glazer JL, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SV, Julius D.\n                      The menthol receptor TRPM8 is the principal detector of environmental cold.\n                      Nature\n                      484\n                      : 204\u2013209, 2007.","DOI":"10.1038\/nature05910"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.068734"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2005.04251.x"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30168"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030377"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.01.008"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Dietrich A\n                      , Kalwa H, Fuchs B, Grimminger F, Weissmann N, Gudermann T.\n                      In vivo TRPC functions in the cardiopulmonary vasculature.\n                      Cell Calcium\n                      43\n                      : 233\u2013244, 2007.","DOI":"10.1016\/j.ceca.2007.02.009"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1994.tb03871.x"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.72.5.2222"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Hawthorn M\n                      , Ferrante J, Luchowski E, Rutledge A, Wei XY, Triggle DJ.\n                      The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations.\n                      Aliment Pharmacol Ther\n                      2\n                      : 101\u2013118, 1988.","DOI":"10.1111\/j.1365-2036.1988.tb00677.x"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000233356.10630.8a"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2008.07.001"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00849.2004"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2221-07.2007"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.77.6.1222"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806651200"},{"key":"R19","unstructured":"Levick JR\n                      .\n                      An Introduction to Cardiovascular Physiology\n                      (4\n                      th\n                      ed.). London: Arnold, 2003."},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Li Y\n                      , Duckles SP.\n                      Effect of age on vascular content of calcitonin gene-related peptide and mesenteric vasodilator nerve activity in the rat.\n                      Eur J Pharmacol\n                      236\n                      : 73\u201378, 1993.","DOI":"10.1016\/0014-2999(93)90474-V"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3632-04.2005"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2006.05.005"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1038\/nature719"},{"key":"R24","unstructured":"Melanaphy D\n                      , Johnson CD, Dickson P, Anderson P, Zholos A.\n                      Characterization of the TRPM8 calcium channel in rat aorta and tail artery.\n                      Proc Physiol Soc\n                      7\n                      : PC2, 2007."},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200506210-00015"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.471bj.x"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01148.2007"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00652-9"},{"key":"R29","unstructured":"Purse A\n                      , Zholos AV, Johnson CD.\n                      A possible role for transient receptor potential (melastatin) 8 (TRPM8) channels in human cutaneous blood flow.\n                      Proc Physiol Soc\n                      11\n                      : C106, 2008."},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1002\/jps.3030460203"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1038\/nn1451"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2005"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90150-3"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503544200"},{"key":"R35","unstructured":"Tsavaler L\n                      , Shapero MH, Morkowski S, Laus R.\n                      Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins.\n                      Cancer Res\n                      61\n                      : 3760\u20133769, 2001."},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4658-03.2004"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142819"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(03)00124-6"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701319"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00515.2005"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-2146"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.01112.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T17:20:07Z","timestamp":1567963207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.01112.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2009,6]]}},"alternative-id":["10.1152\/ajpheart.01112.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.01112.2008","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6]]}}}