The Ca2+-sensing receptor: a target for polyamines

Stephen J. Quinn, Chian-Ping Ye, Rubin Diaz, Olga Kifor, Mei Bai, Peter Vassilev, Edward Brown
1997 American Journal of Physiology - Cell Physiology  
Brown. The Ca 2ϩ -sensing receptor: a target for polyamines. Am. J. Physiol. 273 (Cell Physiol. 42): C1315-C1323, 1997.-The Ca 2ϩsensing receptor (CaR) is activated at physiological levels of external Ca 2ϩ (Ca o ) but is expressed in a number of tissues that do not have well-established roles in the control of Ca o , including several regions of the brain and the intestine. Polyamines are endogenous polyvalent cations that can act as agonists for the CaR, as shown by our current studies of
more » ... rent studies of human embryonic kidney (HEK-293) cells transfected with the human CaR. Cellular parameters altered by polyamines included cytosolic free Ca 2ϩ (Ca i ), inositol phosphate production, and the activity of a nonselective cation channel. Spermine stimulated Ca i transients in CaR-transfected HEK cells, with a concentration producing a half-maximal response (EC 50 ) of ϳ500 µM in the presence of 0.5 mM Ca 2ϩ , whereas sustained increases in Ca i had an EC 50 of ϳ200 µM. The order of potency was spermine Ͼ spermidine ϾϾ putrescine. Elevation of Ca o shifted the EC 50 for spermine sharply to the left, with substantial stimulation below 100 µM. Addition of subthreshold concentrations of spermine increased the sensitivity of CaR-expressing HEK cells to Ca o . Parathyroid hormone secretion from bovine parathyroid cells was inhibited by 50% in the presence of 200 µM spermine, a response similar to that elicited by 2.0 mM Ca o . These data suggest that polyamines could be effective agonists for the CaR, and several tissues, including the brain, may use the CaR as a target for the actions of spermine and other endogenous polycationic agonists. spermine; polycationic agonists; calcium
doi:10.1152/ajpcell.1997.273.4.c1315 fatcat:l5jnjtfxa5abnejulksvyfbmr4