AbstractThese studies examined the importance of phospholipase Cβ (PLCβ) in the calcium responses of pituitary cells using PLCβ3 knockout mice. Pituitary tissue from wild-type mice contained PLCβ1 and PLCβ3 but not PLCβ2 or PLCβ4. Both Gαq/11 and Gβγ can activate PLCβ3, whereas only Gαq/11 activates PLCβ1 effectively. In knockout mice, PLCβ3 was absent, PLCβ1 was not up-regulated, and PLCβ2 and PLCβ4 were not expressed. Since somatostatin inhibited influx of extracellular calcium in pituitary cells from wild-type and PLCβ3 knockout mice, the somatostatin signal pathway was intact. However, somatostatin failed to increase intracellular calcium in pituitary cells from either wild-type or knockout mice under a variety of conditions, indicating that it did not stimulate PLCβ3. In contrast, somatostatin increased intracellular calcium in aortic smooth muscle cells from wild-type mice, although it evoked no calcium response in cells from PLCβ3 knockout animals. These results show that somatostatin, like other Gi/Go-linked hormones, can stimulate a calcium transient by activating PLCβ3 through Gβγ, but this response does not normally occur in pituitary cells. The densities of Gi and Go, as well as the relative concentrations of PLCβ1 and PLCβ3, were similar in cells that responded to somatostatin with an increase in calcium and pituitary cells. Calcium responses to 1 nm and 1μ m TRH and GnRH were identical in pituitary cells from wild-type and PLCβ3 knockout mice, as were responses to other Gq-linked agonists. These results show that in pituitary cells, PLCβ1 is sufficient to transmit signals from Gq-coupled hormones, whereas PLCβ3 is required for the calcium-mobilizing actions of somatostatin observed in smooth muscle cells.