Somatostatin (SS) is a neuropeptide that is distributed in various reg
ions of the CNS, where it may act as a neurotransmitter or neuromodula
tor. SS produces multiple effects in the CNS through interactions with
membrane receptors. In particular, SS inhibits various secretory resp
onses in different cell types. In the present study, we have investiga
ted the effects of exogenous application of SS on the intracellular fr
ee Ca2+ concentration ([Ca2+](i)) in PC12 cells, a rat pheochromocytom
a cell line. SS did reduce the magnitude of the secondary, maintained
Ca2+ influx brought about by K+ depolarization. Similar effects were o
btained with the application of SS analogues, such as D-Trp(8)-SS, D-T
rp(8)-D-Cys(14)-SS, CGP-23996, and SMS-201995. In addition, treatment
with cyclo-SS, a SS antagonist, did not alter [Ca2+](i). Experiments w
ith selective blockers of different voltage-dependent Ca2+ channels, s
uch as methoxyverapamil (D600) and Omega-conotoxin GVIA, demonstrated
that the effects of SS on [Ca2+](i) were mediated by voltage-dependent
Ca2+ channels of the L type. Control experiments with a membrane pote
ntial indicator, i.e., the fluorescent dye bisoxonol, excluded that SS
influenced the level of the membrane potential. SS effects on PC12 ce
lls suggest the possibility that this neuropeptide plays a role in the
modulation of cell functional activity by altering Ca2+ influx.