Somatostatin‐induced control of cytosolic free calcium in pituitary tumour cells

In rat pituitary tumour cells (GC cells), spontaneous oscillations of the intracellular concentration of Ca 2+ ([Ca 2+ ] i ) induce growth hormone (GH) secretion that is inhibited by octreotide, a somatostatin (SRIF) agonist which binds to SRIF subtype (sst) receptor 2. The effects of its functional activation on the control of [Ca 2+ ] i were investigated using fluorimetric measurements of [Ca 2+ ] i . SRIF decreases the basal [Ca 2+ ] i and the [Ca 2+ ] i rise in response to forskolin (FSK) through the inhibition of L‐type voltage‐dependent Ca 2+ channels. Pretreatment with octreotide or with L‐Tyr 8 Cyanamid 154806, a sst 2 receptor antagonist, abolishes the SRIF‐induced inhibition of [Ca 2+ ] i . Octreotide is known to operate through agonist‐induced desensitization, while the antagonist operates through receptor blockade. sst 1 and sst 2 receptor‐immunoreactivities (‐IRs) are localized to cell membranes. sst 2 , but not sst 1 receptor‐IR, internalizes after cell exposure to octreotide. SRIF‐induced inhibition of basal [Ca 2+ ] i or FSK‐induced Ca 2+ entry is blocked by pertussis toxin (PTX). FSK‐induced cyclic AMP accumulation is only partially decreased by SRIF or octreotide, indicating that sst 2 receptors are coupled to intracellular pathways other than adenylyl cyclase (AC) inhibition. In the presence of H‐89, an inhibitor of cyclic AMP‐dependent protein kinase (PKA), SRIF‐induced inhibition of basal [Ca 2+ ] i is still present, although reduced in amplitude. SRIF inhibits [Ca 2+ ] i by activating sst 2 receptors. Inhibition of AC activity is only partly responsible for this effect, and other transduction pathways may be involved.British Journal of Pharmacology (2000) 129 , 471–484; doi: 10.1038/sj.bjp.0703075