{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:43:24Z","timestamp":1789965804041,"version":"4.0.1"},"reference-count":38,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:p>The aim of this study was to evaluate cutaneous vasodilation and sweating responses to exogenous administration of acetylcholine (ACh) and methacholine (MCh), which have different sensitivities to endogenous cholinesterase. Four intradermal microdialysis probes were placed in dorsal forearm skin: two sites were perfused with ACh (1 \u00d7 10<jats:sup>\u22127<\/jats:sup>\u20131 M) and the other two with the same molar concentrations of MCh. Sweat rate (SR) and cutaneous blood flow were simultaneously assessed directly over each microdialysis membrane. Dose-response curves were constructed, and the effective concentration of the drug resulting in 50% of the maximal response (EC<jats:sub>50<\/jats:sub>) was identified. For SR and cutaneous vascular conductance (CVC), there were no significant differences in EC<jats:sub>50<\/jats:sub>between sites receiving the same drug: \u22121.52 \u00b1 0.18 and \u22121.19 \u00b1 0.09 log-molar concentration of ACh at distal and proximal sites, respectively, and \u22122.35 \u00b1 0.24 and \u22122.42 \u00b1 0.23 log-molar concentration of MCh at distal and proximal sites, respectively, for SR ( P &gt; 0.05) and \u22123.87 \u00b1 0.32 and \u22123.97 \u00b1 0.27 log-molar concentration of ACh at distal and proximal sites, respectively, and \u22124.78 \u00b1 0.17 and \u22124.46 \u00b1 0.16 log-molar concentration of MCh at distal and proximal sites, respectively, for CVC ( P &gt; 0.05). However, the EC<jats:sub>50<\/jats:sub>for CVC and SR was significantly lower at the MCh than at the ACh sites. A second procedure was performed to confirm that differences in responses between ACh and MCh could be attributed to different cholinesterase sensitivities. Similarly, four microdialysis membranes were placed in dorsal forearm skin: two sites were perfused with ACh and other two with MCh. However, one of each of the ACh and MCh sites was also perfused with 10 \u03bcM neostigmine (an acetylcholinesterase inhibitor). Neostigmine at the ACh site induced a leftward shift (i.e., lower EC<jats:sub>50<\/jats:sub>) of the SR and CVC dose-response curves compared with the site treated with ACh alone, resulting in no difference in the EC<jats:sub>50<\/jats:sub>for SR and CVC between the ACh + neostigmine and the MCh site. These results suggest that elevations in SR and CVC occur earlier with MCh than with ACh treatment because of differences in cholinesterase susceptibility between these drugs.<\/jats:p>","DOI":"10.1152\/japplphysiol.01069.2006","type":"journal-article","created":{"date-parts":[[2007,1,19]],"date-time":"2007-01-19T01:50:01Z","timestamp":1169171401000},"page":"1856-1861","source":"Crossref","is-referenced-by-count":41,"title":["Cutaneous blood flow and sweat rate responses to exogenous administration of acetylcholine and methacholine"],"prefix":"10.1152","volume":"102","author":[{"given":"Kenichi","family":"Kimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Low","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig G.","family":"Crandall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Andreassen AK, Gullestad L, Holm T, Simonsen S, Kvernebo K.Endothelium-dependent vasodilation of the skin microcirculation in heart transplant recipients.Clin Transplant12: 324\u2013332, 1998.","DOI":"10.1111\/j.1399-0012.1998.tb00977.x"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410290604"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20497"},{"key":"R4","unstructured":"Bickel A, Axelrod FB, Marthol H, Schmelz M, Hilz MJ.Sudomotor function in familial dysautonomia.J Neurol Neurosurg Psychiatry75: 275\u2013279, 2004."},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1080\/10739680490425958"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1046\/j.1087-0024.2000.00010.x"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/jid.1989.2"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/0026-2862(92)90100-4"},{"key":"R9","unstructured":"Brown JH, Taylor P.Muscarinic receptor agonists and antagonists. In:Goodman & Gilman's The Pharmacological Basis of Therapeutics(9th ed.), edited by Hardman JG and Limbird LE. New York: McGraw-Hill, 1996, p. 141\u2013160."},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1959.sp006309"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.07.008"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.069997"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1971.sp009382"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1038\/288373a0"},{"key":"R15","unstructured":"Groth L.Cutaneous microdialysis. Methodology and validation.Acta Dermato-Venerol197: 1\u201361, 1996."},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.080952"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.86.4.1185"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00728.2004"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.3.346"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880160612"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.6.1246"},{"key":"R22","unstructured":"Koppanyi T, Karczmar AG, Sheatz GC.Correlation between pharmacological responses to benzoylcholine, methacholine, and acetylcholine and activity of cholinesterases.J Pharmacol Exp Ther107: 482\u2013500, 1953."},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1986.tb05166.x"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1968.25.3.255"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1042\/cs1010567"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.1.H177"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1038\/327524a0"},{"key":"R28","unstructured":"Pappano A.Cholinoceptor-activating and cholinesterase-inhibiting drugs. In:Basic and Clinical Pharmacology, edited by Katzung B and Stamford C. Stamford, CT: Appleton & Lange, 1998, p. 90\u2013104."},{"key":"R29","unstructured":"Randall WC, Kimura KK.The pharmacology of sweating.Pharmacol Rev7: 365\u2013397, 1955."},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199703000-00015"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.85.3.830"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2002.282.1.H232"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.2.467"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.3.757"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.051102"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00036.2002"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)90415-R"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.1994.1036"}],"container-title":["Journal of Applied Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/japplphysiol.01069.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T02:43:53Z","timestamp":1736736233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/japplphysiol.01069.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2007,5]]}},"alternative-id":["10.1152\/japplphysiol.01069.2006"],"URL":"https:\/\/doi.org\/10.1152\/japplphysiol.01069.2006","relation":{},"ISSN":["8750-7587","1522-1601"],"issn-type":[{"value":"8750-7587","type":"print"},{"value":"1522-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5]]}}}