Somatostatin-induced control of cytosolic free calcium in pituitary tumourcells

1 In rat pituitary tumour cells (GC cells), spontaneous oscillations of the intracellular concentration of Ca2+ ([Ca2+](i)) induce growth hormone (GH) secretion that is inhibited by octreotide. a somatostatin (SRIF) agonist w hich binds to SRIF subtype (sst) receptor 2. The effects of its functional activation on the control of [Ca2+](i) were investigated using fluorimetric measurements of [Ca2+](i). 2 SRIF decreases the basal [Ca2+](i) and the [Ca2+](i) rise in response to forskolin (FSK) through the inhibition of L-type voltage-dependent Ca2+ cha nnels. 3 Pretreatment with octreotide or with L-Tyr(8)Cyanamid 154806, a sst(2) re ceptor antagonist, abolishes the SRIF-induced inhibition of [Ca2+](i). Octr eotide is known to operate through agonist-induced desensitization, while t he antagonist operates through receptor blockade. 4 sst(1) and sst(2) receptor-immunoreactivities (-IRs) are localized to cel l membranes. sst(2), but not sst(1) receptor-IR, internalizes after cell ex posure to octreotide. 5 SRIF-induced inhibition of basal [Ca2+](i) or FSK-induced Ca2+ entry is b locked by pertussis toxin (PTX). 6 FSK-induced cyclic AMP accumulation is only partially decreased by SRIF o r octreotide, indicating that sst(2) receptors are coupled to intracellular pathways other than adenylyl cyclase (AC) inhibition. 7 In the presence of H-89, an inhibitor of cyclic AMP-dependent protein kin ase (PKA), SRIF-induced inhibition of basal [Ca2+](i) is still present, alt hough reduced in amplitude. 8 SRIF inhibits [Ca2+](i) by activating sst(2) receptors. Inhibition of AC activity is only partly responsible for this effect, and other transduction pathways may be involved.