Regulation of parathyroid hypertensive factor secretion by Ca2+ in spontaneously hypertensive rat parathyroid cells.
BACKGROUND
Elevated parathyroid hypertensive factor (PHF) has been suggested to play a causal role in the pathogenesis of hypertension. Previous studies have indicated that PHF secretion is stimulated by low extracellular (EC) Ca2+. Therefore, we hypothesized that the calcium-sensing receptor (CaR) is involved in regulation of PHF release.


METHODS
Parathyroid gland (PTG) organ and cell cultures derived from spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats were exposed to low and normal EC Ca2+ and PHF release measured by ELISA. Expression of CaR protein was assessed by Western blot.


RESULTS
Low EC Ca2+ stimulated both SHR and WKY PTG organ cultures to secrete more PHF, first observable after 60 min incubation. After 4 h, PHF secretion was stimulated (66-fold v 24-fold stimulation for SHR and WKY, respectively). Cultured SHR and WKY parathyroid cells were also stimulated, but to a lesser extent (2.63-fold v 3.75-fold stimulation for SHR and WKY respectively). After 24 h the stimulation by low EC Ca2+ was no longer apparent. Expression of CaR is elevated in the SHR relative to WKY PTG. In both strains expression is higher under conditions of normal (1.5 mmol/L) EC Ca2+ and it increases with incubation time. The apparent suppression of PHF release by normal (1.5 mmol/L) EC Ca2+ is blocked by pre-exposure of the PTG cells to anti-CaR antibody.


CONCLUSIONS
Low EC Ca2+ stimulated rapid PHF release from both SHR and WKY PTG. Changes in CaR expression may account for different sensitivity to EC Ca2+ of the two strains and over time.
Sutherland
Sharla K
SK
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada R6G 2H7.
Benishin
Christina G
CG
D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D002118:Calcium / Q000008:administration & dosage* / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism; D008955:Models, Cardiovascular; D010280:Parathyroid Glands / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044169:Receptors, Calcium-Sensing / Q000008:administration & dosage; D013997:Time Factors
D001685:Biological Factors; D044169:Receptors, Calcium-Sensing; C064505:parathyroid hypertensive factor; D002118:Calcium