{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T19:47:08Z","timestamp":1772826428970,"version":"3.50.1"},"reference-count":76,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:p> It has been suggested that pesticide exposure may be a contributing factor underlying the increased incidence of asthma in the United States and other industrialized nations. To test this hypothesis, airway hyperreactivity was measured in guinea pigs exposed to chlorpyrifos, a widely used organophosphate pesticide. Electrical stimulation of the vagus nerves caused frequency-dependent bronchoconstriction that was significantly potentiated in animals 24 h or 7 days after a single subcutaneous injection of either 390 mg\/kg or 70 mg\/kg of chlorpyrifos, respectively. Mechanisms by which chlorpyrifos may cause airway hyperreactivity include inhibition of acetylcholinesterase (AChE) or dysfunction of M3 muscarinic receptors on airway smooth muscle or of autoinhibitory M2 muscarinic receptors on parasympathetic nerves in the lung. AChE activity in the lung was significantly inhibited 24 h after treatment with 390 mg\/kg of chlorpyrifos, but not 7 days after injection of 70 mg\/kg of chlorpyrifos. Acute exposure to eserine (250 \u03bcg\/ml) also significantly inhibited lung AChE but did not potentiate vagally induced bronchoconstriction. Neuronal M2 receptor function was tested using the M2 agonist pilocarpine, which inhibits vagally induced bronchoconstriction in control animals. In chlorpyrifos-treated animals, pilocarpine dose-response curves were shifted significantly to the right, demonstrating decreased responsiveness of neuronal M2 receptors. In contrast, chlorpyrifos treatment did not alter methacholine-induced bronchoconstriction, suggesting that chlorpyrifos does not alter M3 muscarinic receptor function on airway smooth muscle. These data demonstrate that organophosphate insecticides can cause airway hyperreactivity in the absence of AChE inhibition by decreasing neuronal M2 receptor function. <\/jats:p>","DOI":"10.1152\/ajplung.00343.2003","type":"journal-article","created":{"date-parts":[[2004,4,2]],"date-time":"2004-04-02T01:29:08Z","timestamp":1080869348000},"page":"L963-L969","source":"Crossref","is-referenced-by-count":75,"title":["Mechanisms of organophosphate insecticide-induced airway hyperreactivity"],"prefix":"10.1152","volume":"286","author":[{"given":"Allison D.","family":"Fryer","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela J.","family":"Lein","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela S.","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany L.","family":"Yost","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rondell A.","family":"Beckles","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Jett","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.2570070210"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.01109583"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1136\/oem.59.8.505"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.112854"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1992.263.1.L142"},{"key":"REF6","doi-asserted-by":"crossref","unstructured":"Berkowitz GS, Obel J, Deych E, Lapinski R, Godbold J, Liu Z, Landrigan PJ, and Wolff MS. Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort. Environ Health Perspect 111: 79-84, 2003.","DOI":"10.1289\/ehp.5619"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(00)00294-0"},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1006\/taap.2001.9324"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00934.2001"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1007\/s003950170003"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.3109\/08037059609078071"},{"key":"REF12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.1985.tb02740.x"},{"key":"REF13","unstructured":"Bushnell PJ, Padilla SS, Ward T, Pope CN, and Olszyk VB. Behavioral and neurochemical changes in rats dosed repeatedly with diisopropylfluorophosphate. J Pharmacol Exp Ther 256: 741-750, 1991."},{"key":"REF14","unstructured":"Casarett LJ and Doull J. Toxicology. New York: Macmillan, 1975."},{"key":"REF15","unstructured":"CDC. Second National Report on Human Exposure to Environmental Chemicals. Atlanta, GA: National Center for Environmental Health, 2003."},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)00004-J"},{"key":"REF17","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.98106299"},{"key":"REF18","doi-asserted-by":"crossref","unstructured":"Delfino RJ, Gong H Jr, Linn WS, Pellizzari ED, and Hu Y. Asthma symptoms in Hispanic children and daily ambient exposures to toxic and criteria air pollutants. Environ Health Perspect 111: 647-656, 2003.","DOI":"10.1289\/ehp.5992"},{"key":"REF19","doi-asserted-by":"crossref","unstructured":"Deschamps D, Questel F, Baud FJ, Gervais P, and Dally S. Persistent asthma after acute inhalation of organophosphate insecticide. Lancet 344: 1712, 1994.","DOI":"10.1016\/S0140-6736(94)90498-7"},{"key":"REF20","doi-asserted-by":"crossref","unstructured":"Dong W, Gilmour MI, Lambert AL, and Selgrade MK. Enhanced allergic responses to house dust mite by oral exposure to carbaryl in rats. Toxicol Sci 44: 63-69, 1998.","DOI":"10.1093\/toxsci\/44.1.63"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.113671"},{"key":"REF22","unstructured":"Eldefrawi AT, Jett DA, and Eldefrawi ME. Direct actions of organophosphate anticholinesterases on muscarinic receptors. In: Organophosphates: Chemistry, Fate and Effects, edited by Chambers JE and Levi PE. New York: Academic, 1992, p. 419-432."},{"key":"REF23","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(61)90145-9"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.5.2201001c"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.99107s3409"},{"key":"REF26","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.02110549"},{"key":"REF27","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.15.6.8969265"},{"key":"REF28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1984.tb16539.x"},{"key":"REF29","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.71.6.2255"},{"key":"REF30","unstructured":"Gallo MA and Lawryk NJ. Organic phosphorus pesticides. In: Handbook of Pesticide Toxicology, edited by Hayes WJ and Laws ER. New York: Academic, 1991, p. 917-972."},{"key":"REF31","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1994.77.3.1492"},{"key":"REF32","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.64.5.1786"},{"key":"REF33","doi-asserted-by":"publisher","DOI":"10.1097\/00063198-200001000-00002"},{"key":"REF34","doi-asserted-by":"publisher","DOI":"10.1006\/enrs.1995.1071"},{"key":"REF35","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.165.5.2106074"},{"key":"REF36","unstructured":"Huff RA, Corcoran JJ, Anderson JK, and Abou-Donia MB. Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum. J Pharmacol Exp Ther 269: 329-335, 1994."},{"key":"REF37","doi-asserted-by":"crossref","unstructured":"Jacoby DB and Fryer AD. Virus-induced airway hyperresponsiveness\u2013possible involvement of neural mechanisms. Am Rev Respir Dis 144: 1422-1423, 1991.","DOI":"10.1164\/ajrccm\/144.6.1422a"},{"key":"REF38","doi-asserted-by":"publisher","DOI":"10.1016\/0048-3575(91)90135-9"},{"key":"REF39","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4274(94)90186-4"},{"key":"REF40","doi-asserted-by":"publisher","DOI":"10.1080\/15287399309531760"},{"key":"REF41","doi-asserted-by":"publisher","DOI":"10.1002\/ajim.10201"},{"key":"REF42","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1997.8201"},{"key":"REF43","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(89)90217-2"},{"key":"REF44","unstructured":"Katz LS and Marquis JK. Organophosphate-induced alterations in muscarinic receptor binding and phosphoinositide hydrolysis in the human SK-N-SH cell line. Neurotoxicology 13: 365-378, 1992."},{"key":"REF45","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.02110829"},{"key":"REF46","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07397-8"},{"key":"REF47","unstructured":"Konieczny B, Kossmann S, and Makuch M. Impaired respiratory muscle function in chemical plant workers producing chlorfenvinphos. Ann Agric Environ Med 6: 21-25, 1999."},{"key":"REF48","unstructured":"Landrigan PJ, Claudio L, Markowitz SB, Berkowitz GS, Brenner BL, Romero H, Wetmur JG, Matte TD, Gore AC, Godbold JH, and Wolff MS. Pesticides and inner-city children: exposures, risks, and prevention. Environ Health Perspect 107, Suppl 3: 431-437, 1999."},{"key":"REF49","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.02110721"},{"key":"REF50","doi-asserted-by":"crossref","unstructured":"Lu C, Knutson DE, Fisker-Andersen J, and Fenske RA. Biological monitoring survey of organophosphorus pesticide exposure among preschool children in the Seattle metropolitan area. Environ Health Perspect 109: 299-303, 2001.","DOI":"10.1289\/ehp.01109299"},{"key":"REF51","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(88)80947-5"},{"key":"REF52","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(91)90117-L"},{"key":"REF53","unstructured":"Mileson BE, Chambers JE, Chen WL, Dettbarn W, Ehrich M, Eldefrawi AT, Gaylor DW, Hamernik K, Hodgson E, Karczmar AG, Padilla S, Pope CN, Richardson RJ, Saunders DR, Sheets LP, Sultatos LG, and Wallace KB. Common mechanism of toxicity: a case study of organophosphorus pesticides. Toxicol Sci 41: 8-20, 1998."},{"key":"REF54","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1988.64.6.2532"},{"key":"REF55","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.67.6.2461"},{"key":"REF56","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13486.x"},{"key":"REF57","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(96)00458-3"},{"key":"REF58","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.12.1638"},{"key":"REF59","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)07222-4"},{"key":"REF60","unstructured":"Overstreet DH. Organophosphate pesticides, cholinergic function and cognitive performance in advanced age. Neurotoxicology 21: 75-81, 2000."},{"key":"REF61","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.02110197"},{"key":"REF62","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(92)90523-I"},{"key":"REF63","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(91)90061-5"},{"key":"REF64","doi-asserted-by":"publisher","DOI":"10.1006\/taap.2002.9445"},{"key":"REF65","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.99107s3393"},{"key":"REF66","doi-asserted-by":"publisher","DOI":"10.1007\/s002109900101"},{"key":"REF67","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/146.4.884"},{"key":"REF68","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(90)90320-T"},{"key":"REF69","unstructured":"Sirajuddin H, Roslinah A, Rampal KG, Kuppusamy I, Rohna R, Aziz M, Aw TC, and Beach JR. Notification of occupational and work-related diseases and poisonings in Malaysia, 1997\u20131998. Med J Malaysia 56: 25-31, 2001."},{"key":"REF70","unstructured":"Stanton ME, Mundy WR, Ward T, Dulchinos V, and Barry CC. Time-dependent effects of acute chlorpyrifos administration on spatial delayed alternation and cholinergic neurochemistry in weanling rats. Neurotoxicology 15: 201-208, 1994."},{"key":"REF71","unstructured":"USDA. Agricultural chemicals and production technology. Washington, DC: Economic Research Service, 2003."},{"key":"REF72","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(95)02044-6"},{"key":"REF73","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(93)90234-8"},{"key":"REF74","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.02110507"},{"key":"REF75","unstructured":"Wilhoit L, Davidson N, Supkoff D, Steggal J, Braun A, Simmons S, Hobza B, Hunter C, Gorder N, Goodman C, and Todd B. Pesticide Use Analysis and Trends from 1991 to 1996. Sacramento, CA: State of California Environmental Protection Agency, 1999."},{"key":"REF76","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.02.00028602"}],"container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajplung.00343.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T23:27:33Z","timestamp":1567985253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajplung.00343.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,5]]},"references-count":76,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2004,5]]}},"alternative-id":["10.1152\/ajplung.00343.2003"],"URL":"https:\/\/doi.org\/10.1152\/ajplung.00343.2003","relation":{},"ISSN":["1040-0605","1522-1504"],"issn-type":[{"value":"1040-0605","type":"print"},{"value":"1522-1504","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,5]]}}}