Substance P increases intracellular Ca2+ in individual rat pituitary lactotrophs, somatotrophs, and gonadotrophs.
The present study has investigated transients in the intracellular calcium concentration [Ca2+]i in response to substance P (SP) in single pituitary cells. SP raised [Ca2+]i in three subtypes of pituitary cells: lactotrophs, somatotrophs, and gonadotrophs. In all three cell subtypes the [Ca2+]i response to SP was amplitude-modulated and a concentration of 100 nM was necessary to elicit well pronounced two phased [Ca2+]i transients. The first phase was associated with increased generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) in all three cell types. In lactotrophs, the second phase, but not the first, was blunted by depletion of extracellular Ca2+ (Ca2+ free EGTA incubation buffer) and by addition of dopamine (1 microM). In somatotrophs, the second phase of the SP-induced [Ca2+]i response was inhibited by depletion of extracellular Ca2+ and by addition of somatostatin (100 nM), while the first phase was unaffected by this treatment. In gonadotrophs, the second phase, but not the first, was inhibited by the Ca2+ channel blocker methoxyverapamil and depletion of extracellular Ca2+. SP was compared with other agonists having an action on lactotrophs, somatotrophs or gonadotrophs. These experiments demonstrated that SP was a weaker agonist in terms of maximal [Ca2+]i response than thyrotropin-releasing hormone (TRH) (in lactotrophs), growth hormone-releasing hexapeptide (in somatotrophs) and GnRH (in gonadotrophs). On the basis of these results it is concluded that SP exerts direct Ca2+ mobilizing effects in single lactotrophs, somatotrophs, and gonadotrophs derived from male peripubertal rats. The first phase in SP-induced [Ca2+]i transients is likely to be brought about by inositol 1,4,5-trisphosphate-mediated Ca2+ release from internal stores while the second phase reflects an influx of calcium through voltage-gated calcium channels.
Mau
S E
SE
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark. smau@pop.mfi.ku.dk
Witt
M R
MR
Saermark
T
T
Vilhardt
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D002118:Calcium