Cocaine- and amphetamine-regulated transcript peptide modulation of voltage-gated Ca2+ signaling in hippocampal neurons.
Administration of cocaine and amphetamine increases cocaine- and amphetamine-regulated transcript (CART) expression in the rat striatum (Douglass et al., 1995). CART mRNA is highly expressed in different parts of the human and rat brain, including hippocampus (Douglass et al., 1995; Couceyro et al., 1997; Kuhar and Yoho, 1999; Hurd and Fagergren, 2000). The presence of CART peptide 55-102 immunoreactivity in dense core vesicles of axon terminals suggests that the peptide may be released and may act as a neuromodulator (Smith et al., 1997) to induce neurophysiological and behavioral effects. Little is known, however, about CART peptide-responsive cells, receptor(s), or intracellular signaling mechanisms that mediate CART peptide action. Here we show that CART peptide 55-102 inhibits voltage-dependent intracellular Ca(2+) signaling and attenuates cocaine enhancement of depolarization-induced Ca(2+) influx in rat hippocampal neurons. The inhibitory effect of CART peptide 55-102 on Ca(2+) signaling is likely mediated by an inhibition of L-type voltage-gated Ca(2+) channel activity via a G-protein-dependent pathway. These results indicate that voltage-gated Ca(2+) channels in hippocampal neurons are targets for CART peptide 55-102 and suggest that CART peptides may be important in physiology and behavior mediated by the hippocampus, such as certain forms of learning and memory.
Yermolaieva
O
O
Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, USA.
Chen
J
J
Couceyro
P R
PR
Hoshi
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D003042:Cocaine; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D019204:GTP-Binding Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011188:Potassium; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein