{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:58:36Z","timestamp":1760061516867},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,9,6]],"date-time":"2004-09-06T00:00:00Z","timestamp":1094428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Research"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p>Gravity alteration (micro\u2010 and hypergravity) is known to influence cell functions. As guanosine 3\u2032,5\u2032\u2010cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non\u2010metastatic and metastatic melanoma cells, we investigated the effects of hypergravity on the regulation of cGMP levels in cultured human melanocytes and in melanoma cell lines with different metastatic potentials. Hypergravity was produced by horizontal centrifugal acceleration. Here we report that long\u2010term application of hypergravity (up to 5\u2003<jats:italic>g<\/jats:italic> for 24\u2003h) stimulated cGMP efflux in cultured melanocytes and in non\u2010metastatic melanoma cells in the presence of 0.1\u2003mM 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX), a non\u2010selective phosphodiesterase (PDE) inhibitor. Under these conditions, cAMP synthesis and melanin production were up\u2010regulated in pigmented melanocytes and non\u2010metastatic melanoma cells. Hypergravity also stimulated cGMP transport in the presence of 1\u2003<jats:italic>\u03bc<\/jats:italic>M trequinsin, an inhibitor of cGMP\u2010binding PDE (PDE5) and of transport by multidrug resistance proteins MRP4\/5, whereas 50\u2003<jats:italic>\u03bc<\/jats:italic>M trequinsin partially inhibited cGMP transport. Transport was further inhibited by probenecid, an inhibitor of endogenous non\u2010selective transporters as well as of MRP4\/5 and by cycloheximide as an inhibitor of de novo protein synthesis. In contrast, hypergravity did not affect cGMP efflux in metastatic melanoma cells, which might be related to an up\u2010regulated cGMP efflux at 1\u2003<jats:italic>g<\/jats:italic>. The results of the present study indicate that hypergravity may stimulate cGMP efflux in melanocytes and in non\u2010metastatic melanoma cells most probably by an enhanced expression of endogenous transporters and\/or MRP4\/5. Thus, an altered acceleration vector may induce signaling events in melanocytic cells.<\/jats:p>","DOI":"10.1111\/j.1600-0749.2004.00169.x","type":"journal-article","created":{"date-parts":[[2004,9,6]],"date-time":"2004-09-06T16:14:41Z","timestamp":1094487281000},"page":"471-479","source":"Crossref","is-referenced-by-count":9,"title":["Stimulation of Cyclic GMP Efflux in Human Melanocytes by Hypergravity Generated by Centrifugal Acceleration"],"prefix":"10.1111","volume":"17","author":[{"given":"Krassimira","family":"Ivanova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahid Hamidi","family":"Zadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Block","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranab K.","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rupert","family":"Gerzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,9,6]]},"reference":[{"key":"e_1_2_15_2_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1242\/jcs.97.1.33","article-title":"Microgravity decreases c\u2010fos induction and serum response element activity","volume":"97","author":"Groot RP","year":"1990","journal-title":"J Cell Sci"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(91)90483-B"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1247\/csf.23.221"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.9001.s129"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.23.1258"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5986"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11328"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7364.567"},{"key":"e_1_2_15_10_2","first-page":"450","article-title":"UVA\/B and mechanical pressure induce melanin formation by human melanocytes in culture","volume":"2","author":"Bernd A","year":"1992","journal-title":"Eur J Dermatol"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.1999.tb00757.x"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2000.130410.x"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.45.28052"},{"key":"e_1_2_15_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90267-4"},{"key":"e_1_2_15_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00084.x"},{"key":"e_1_2_15_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(81)80429-2"},{"key":"e_1_2_15_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1990.tb00772.x"},{"key":"e_1_2_15_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.01255.x"},{"key":"e_1_2_15_19_2","first-page":"P271","article-title":"Gravity and cyclic GMP levels in melanocytic cells","volume":"9","author":"Ivanova K","year":"2002","journal-title":"J Gravit Physiol"},{"key":"e_1_2_15_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm911"},{"key":"e_1_2_15_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005463200"},{"key":"e_1_2_15_22_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3610497"},{"key":"e_1_2_15_23_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V133595"},{"key":"e_1_2_15_24_2","first-page":"3338","article-title":"Exisulind induction of apoptosis involves guanosine 3\u2032,5\u2032\u2010cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation, and attenuated beta\u2010catenin","volume":"60","author":"Thompson WJ","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_15_25_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0075"},{"key":"e_1_2_15_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(99)00184-4"},{"key":"e_1_2_15_27_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.5.1317"},{"key":"e_1_2_15_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(99)00071-4"},{"key":"e_1_2_15_29_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68041451.x"},{"key":"e_1_2_15_30_2","first-page":"99","article-title":"Extracellular 3\u2032,5\u2032 cyclic guanosine monophosphate inhibits kainite\u2010activated responses in cultured mouse cerebellar neurons","volume":"286","author":"Poulopoulou C","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_15_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01753729"},{"key":"e_1_2_15_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910540225"},{"key":"e_1_2_15_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.12.7284"},{"key":"e_1_2_15_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0273-1177(95)00646-V"},{"key":"e_1_2_15_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/15321819508013548"},{"key":"e_1_2_15_36_2","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1681\/ASN.V103472","article-title":"cGMP\u2010dependent and \u2013 independent inhibition of a K+ conductance by natriuretic peptides: Molecular and functional studies in human proximal tubule cells","volume":"10","author":"Hirsch JR","year":"1999","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_15_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_15_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-91-5-1180"},{"key":"e_1_2_15_39_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.141.7.2407"},{"key":"e_1_2_15_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212723200"},{"key":"e_1_2_15_41_2","first-page":"919","article-title":"Signaling pathways mediating melanogenesis","volume":"45","author":"Park HY","year":"1999","journal-title":"Cell Mol Biol"},{"key":"e_1_2_15_42_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2000.130203.x"}],"container-title":["Pigment Cell Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0749.2004.00169.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0749.2004.00169.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T17:50:01Z","timestamp":1697305801000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0749.2004.00169.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,9,6]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2004,10]]}},"alternative-id":["10.1111\/j.1600-0749.2004.00169.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0749.2004.00169.x","archive":["Portico"],"relation":{},"ISSN":["0893-5785","1600-0749"],"issn-type":[{"value":"0893-5785","type":"print"},{"value":"1600-0749","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,9,6]]}}}