ACUTE STIMULATION OF INTESTINAL-CELL CALCIUM INFLUX INDUCED BY 17-BETA-ESTRADIOL VIA THE CAMP MESSENGER SYSTEM

Recent studies have provided evidence for nuclear estrogen receptor-me diated calcium transport in intestinal mucosal cells. The possibility that, in addition, estrogens directly stimulate intestinal Ca2+ flu?re s through second-messenger pathways was investigated. Exposure of ente rocytes isolated from female rat duodenum to low physiological levels of 17 beta-estradiol (10(-11), 10(-10) and 10(-8) M) rapidly (1-10 min ) increased (50-170%) cell Ca-45(2+) influx. 17 alpha-Estradiol, dihyd rotestosterone and progesterone were devoid of activity, suggesting sp ecificity of the estrogen effect. Maximum responses induced by 17 beta -estradiol (5 min at 10(-10) M) could be abolished to a great extent ( 84%) by pretreating the cells with verapamil (10 mu M) and nitrendipin e (1 mu M), involving the activation of voltage-dependent Ca2+ channel s in the fast increase of rat duodenal calcium uptake by the hormone. Evidence was obtained indicating that the acute estrogen stimulation o f enterocyte Ca2+ influx is mediated by the cyclic AMP/PKA pathway. 17 beta-Estradiol rapidly increased cAMP content of rat duodenal cells i n parallel to the changes in Ca2+ uptake. In addition, forskolin, dibu tyryl cAMP and Sp-cAMPS mimicked and Rp-cAMPS suppressed the prompt 17 beta-estradiol-induced stimulation of Ca2+ influx. These results are consistent with a direct action of estrogens in the enterocyte, presum ably a non-genomic one, initiated on the cell surface and resulting in rapid activation of the cAMP pathway and Ca2+ channels, which may be relevant for regulation of intestinal calcium transport.