Va. Romoser et al., Calcium responses to thyrotropin-releasing hormone, gonadotropin-releasinghormone and somatostatin in phospholipase C beta 3 knockout mice, MOL ENDOCR, 15(1), 2001, pp. 125-135
These studies examined the importance of phospholipase C beta (PLC beta) in
the calcium responses of pituitary cells using PLC beta3 knockout mice. Pi
tuitary tissue from wild-type mice contained PLC beta1 and PLC beta3 but no
t PLC beta2 or PLC beta4. Both G alphaq/11 and G beta gamma can activate PL
C beta3, whereas only G alphaq/11 activates PLC beta1 effectively. In knock
out mice, PLC beta3 was absent, PLC beta1 was not up-regulated, and PLC bet
a2 and PLC beta4 were not expressed. Since somatostatin inhibited influx of
extracellular calcium in pituitary cells from wild-type and PLC beta3 knoc
kout mice, the somatostatin signal pathway was intact. However, somatostati
n failed to increase intracellular calcium in pituitary cells from either w
ild-type or knockout mice under a variety of conditions, indicating that it
did not stimulate PLC beta3. In contrast, somatostatin increased intracell
ular calcium in aortic smooth muscle cells from wild-type mice, although it
evoked no calcium response in cells from PLC beta3 knockout animals. These
results show that somatostatin, like other Gi/Go-linked hormones, can stim
ulate a calcium transient by activating PLC beta3 through G beta gamma, but
this response does not normally occur in pituitary cells. The densities of
Gi and Go, as well as the relative concentrations of PLC beta1 and PLC bet
a3, were similar in cells that responded to somatostatin with an increase i
n calcium and pituitary cells. Calcium responses to 1 nM and 1 muM TRH and
GnRH were identical in pituitary cells from wild-type and PLC beta3 knockou
t mice, as were responses to other Gq-linked agonists. These results show t
hat in pituitary cells, PLC beta1 is sufficient to transmit signals from Gq
-coupled hormones, whereas PLC beta3 is required for the calcium-mobilizing
actions of somatostatin observed in smooth muscle cells.