Expression and activity of cocaine- and amphetamine-regulated transcript peptide(1-39) in the rat.
Cocaine- and amphetamine-regulated transcript (CART) peptide consists of a family of peptides. Expression of the peptide fragment CART(1-39) was explored in the rat using an antiserum directed against CART(1-39) of the short form of the human CART prohormone. CART(1-39)-immunoreactivity, herein referred to as irCART, was detected in the rat central and peripheral nervous tissues with a pattern similar to that labeled with the antiserum CART(55-102) or CART(79-102). For example, irCART cells were detected in the hypothalamus, pons, medulla oblongata, spinal cord, and adrenal medulla. In urethane-anesthetized rats, CART(1-39) (0.05 to 2 nmol) by intrathecal injection did not cause a significant change of blood pressure or heart rate, but potentiated the pressor effects of glutamate injected intrathecally. Lastly, the effect of CART(1-39) on intracellular calcium concentrations [Ca2+]i was assessed and compared to that caused by CART(55-102) in cultured rat cortical neurons using the microfluorimetric method. CART(1-39) (100 nM) induced two types of responses in a population of cortical neurons: 1) a slowly rising increase in [Ca2+]i superimposed with oscillations, and 2) a fast increase followed by a sustained increase of [Ca2+]i. CART(55-102) caused only a slowly rising increase in [Ca2+]i in cortical neurons. Our result shows that the expression pattern of irCART in the rat nervous system and the potentiating action of CART(1-39) on glutamate-induced pressor response is similar to that reported for CART(55-102); but the calcium mobilizing action of CART(1-39) differs from that of CART(55-102), suggesting the possible existence of multiple CART receptors coupled to different calcium signaling pathways.
Dun
Siok L
SL
Department of Pharmacology, Temple University School of Medicine, 3400 N. Broad Street, Philadelphia, PA 19140, USA.
Brailoiu
Eugen
E
Hsieh
Wei-Kung
WK
Lai
Chih-Chia
CC
Yang
Jun
J
Chang
Jaw Kang
JK
Dun
Nae J
NJ
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005724:Ganglia / Q000378:metabolism; D018698:Glutamic Acid / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D007278:Injections, Spinal; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C428723:cocaine- and amphetamine-regulated transcript protein (55-102); D018698:Glutamic Acid; D002118:Calcium