Cromakalim: embryonic effects and reduction of tolbutamide‐induced dysmorphogenesis in vitro

TeratologyVolume 60, Issue 5 p. 260-264 Research Article Cromakalim: embryonic effects and reduction of tolbutamide-induced dysmorphogenesis in vitro Ida W. Smoak, Corresponding Author Ida W. Smoak [email protected] Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina 27606Department of Anatomy, Physiological Sciences, and Radiology, 4700 Hillsborough Street, Raleigh, NC 27606.Search for more papers by this author Ida W. Smoak, Corresponding Author Ida W. Smoak [email protected] Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina 27606Department of Anatomy, Physiological Sciences, and Radiology, 4700 Hillsborough Street, Raleigh, NC 27606.Search for more papers by this author First published: 18 October 1999 https://doi.org/10.1002/(SICI)1096-9926(199911)60:5<260::AID-TERA6>3.0.CO;2-PCitations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Cromakalim is a K+ channel opener that causes smooth muscle relaxation by activating ATP-sensitive K+ (KATP) channels and producing membrane hyperpolarization. Cromakalim counteracts sulfonylurea-induced KATP channel inhibition in adult cells, but little is known regarding its embryonic effects, alone or in combination with sulfonylureas. KATP channels have been demonstrated in the embryo, but their role in normal and abnormal development is unknown. Early-somite mouse embryos were exposed for 24 hr in vitro to cromakalim at concentrations of 0 (Cntl), 1, 10, 100, 200, or 500 μM in 0.125% DMSO. Embryos were also exposed for 24 hr in vitro to a dysmorphogenic tolbutamide concentration (110 μg/ml) combined with a subdysmorphogenic concentration of cromakalim (1 μM). Embryos were evaluated for somite number, heart rate, malformations, and embryonic and yolk sac protein content. Embryos exposed to 1 μM cromakalim were similar to controls. Cromakalim exposure increased malformation rates at concentrations ≥200 μM, decreased heart rates at ≥10 μM, and decreased somite and protein values at 500 μM. Defects involved cranial neural tube, optic vesicle, heart, and somites. A malformation rate of 59% in embryos exposed to 110 μg/ml tolbutamide was reduced to 13% by adding 1 μM cromakalim to the culture medium. Heart rate, somite number, and protein values were also improved by combined exposure to cromakalim and tolbutamide compared with exposure to tolbutamide alone. These results support previous findings with diazoxide (K+ channel opener) and chlorpropamide (sulfonylurea) and further suggest a potential role for KATP channel effects in sulfonylurea-induced dysmorphogenesis. Teratology 60:260–264, 1999. © 1999 Wiley-Liss, Inc. LITERATURE CITED Ban Y, Konishi R, Kawana K, Nakatsuka T, Fujii T, Manson JM. 1994. 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