Somatostatin-14 and somatostatin-28 induce opposite effects on potassium currents in rat neocortical neurons.
The prosomatostatin-derived peptides somatostatin-14 (Som-14) and somatostatin-28 (Som-28) are believed to act as neurotransmitters in the central nervous system. To examine possible mechanisms by which these peptides induce their physiological actions in brain, the effects of Som-14 and Som-28 on voltage-dependent K+ currents in rat cerebral cortical neurons in culture were examined by using whole-cell patch-clamp techniques. Som-14 increased a delayed rectifier K+ current (IK) in the cortical neurons, while Som-28 reduced IK in the neurons, both in a concentration-dependent manner. Som-14 and Som-28 could induce opposite changes in IK in the same neurons. Elevating intracellular cAMP in the cortical neurons did not modify the effects of Som-14 or Som-28 on IK, indicating that the peptides can regulate this ionic current through cAMP-independent mechanisms. Pretreatment of the neocortical cells with pertussis toxin, which inactivates inhibitory GTP-binding proteins, abolished both Som-14 and Som-28 modulation of IK, indicating that Som-14 and Som-28 receptors are coupled to IK via GTP-binding proteins. These studies show that Som-14 and Som-28 can induce opposite biological effects, suggesting that Som-14 and Som-28, acting through distinct receptors, may function as different neurotransmitters or neuromodulators.
Wang
H L
HL
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Bogen
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C
Reisine
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Dichter
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D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D053561:Somatostatin-28
D015221:Potassium Channels; D011498:Protein Precursors; D013004:Somatostatin; D053561:Somatostatin-28