Expression and activity of cocaine- and amphetamine-regulated transcript peptide1-39 in the rat

Cocaine- and amphetamine-regulated transcript (CART) peptide consists of a family of peptides. Expression of the peptide fragment CART1-39 was explored in the rat using an antiserum directed against CART1-39 of the short form of the human CART prohormone. CART1-39-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 CART55-102 or CART79-102. For example, irCART cells were detected in the hypothalamus, pons, medulla oblongata, spinal cord, and adrenal medulla. In urethane-anesthetized rats, CART1-39 (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 CART1-39 on intracellular calcium concentrations [Ca2+]i was assessed and compared to that caused by CART55-102 in cultured rat cortical neurons using the microfluorimetric method. CART1-39 (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. CART55-102 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 CART1-39 on glutamate-induced pressor response is similar to that reported for CART55-102; but the calcium mobilizing action of CART1-39 differs from that of CART55-102, suggesting the possible existence of multiple CART receptors coupled to different calcium signaling pathways.