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

✍ Scribed by Smoak, Ida W.

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 142 KB
• Volume: 60
• Category: Article
• ISSN: 0040-3709
• DOI: 10.1002/(sici)1096-9926(199911)60:5<260::aid-tera6>3.0.co;2-p

✦ Synopsis

Cromakalim is a K ϩ channel opener that causes smooth muscle relaxation by activating ATP-sensitive K ϩ (K ATP ) channels and producing membrane hyperpolarization. Cromakalim counteracts sulfonylurea-induced K ATP channel inhibition in adult cells, but little is known regarding its embryonic effects, alone or in combination with sulfonylureas. K ATP 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 M in 0.125% DMSO. Embryos were also exposed for 24 hr in vitro to a dysmorphogenic tolbutamide concentration (110 g/ml) combined with a subdysmorphogenic concentration of cromakalim (1 M). Embryos were evaluated for somite number, heart rate, malformations, and embryonic and yolk sac protein content. Embryos exposed to 1 M cromakalim were similar to controls. Cromakalim exposure increased malformation rates at concentrations Ն200 M, decreased heart rates at Ն10 M, and decreased somite and protein values at 500 M. Defects involved cranial neural tube, optic vesicle, heart, and somites. A malformation rate of 59% in embryos exposed to 110 g/ml tolbutamide was reduced to 13% by adding 1 M 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 ϩ channel opener) and chlorpropamide (sulfonylurea) and further suggest a potential role for K ATP channel effects in sulfonylurea-induced dysmorphogenesis.