TY - JOUR
T1 - Cocaine- and amphetamine-regulated transcript peptide modulation of voltage-gated Ca2+ signaling in hippocampal neurons
AU - Yermolaieva, Olena
AU - Chen, Jianguo
AU - Couceyro, Pastor R.
AU - Hoshi, Toshinori
PY - 2001/10/1
Y1 - 2001/10/1
N2 - 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 Ca2+ signaling and attenuates cocaine enhancement of depolarization-induced Ca2+ influx in rat hippocampal neurons. The inhibitory effect of CART peptide 55-102 on Ca2+ signaling is likely mediated by an inhibition of L-type voltage-gated Ca2+ channel activity via a G-protein-dependent pathway. These results indicate that voltage-gated Ca2+ 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.
AB - 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 Ca2+ signaling and attenuates cocaine enhancement of depolarization-induced Ca2+ influx in rat hippocampal neurons. The inhibitory effect of CART peptide 55-102 on Ca2+ signaling is likely mediated by an inhibition of L-type voltage-gated Ca2+ channel activity via a G-protein-dependent pathway. These results indicate that voltage-gated Ca2+ 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.
KW - CART
KW - Calcium
KW - Cocaine
KW - Hippocampus
KW - Neuropeptide
KW - Voltage-gated calcium channels
UR - http://www.scopus.com/inward/record.url?scp=0035478016&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.21-19-07474.2001
DO - 10.1523/jneurosci.21-19-07474.2001
M3 - Article
C2 - 11567037
AN - SCOPUS:0035478016
SN - 0270-6474
VL - 21
SP - 7474
EP - 7480
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 19
ER -