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.