Expression and activity of cocaine- and amphetamine-regulated transcript peptide 1–39 in the rat

Abstract

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 [Ca 2+] 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 [Ca 2+] i superimposed with oscillations, and 2) a fast increase followed by a sustained increase of [Ca 2+] i. CART 55–102 caused only a slowly rising increase in [Ca 2+] 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.