Cocaine- and amphetamine-regulated transcript peptide potentiates spinal glutamatergic sympathoexcitation in anesthetized rats.
Cocaine- and amphetamine-regulated transcript (CART) is widely expressed in the rat central nervous system, notably in areas involved in control of autonomic and neuroendocrine functions. The aim of this study was to evaluate the effects of CART peptide fragment 55-102, referred to herein as CARTp, by intrathecal injection on blood pressure (BP) and heart rate (HR) before and after intrathecal glutamate in urethane-anesthetized male Sprague-Dawley rats. CARTp (0.1-10 nmol) administered intrathecally caused no or a small, statistically insignificant increase of blood pressure and heart rate, except at the concentration of 10 nmol, which caused a significant increase of blood pressure and heart rate. Intrathecal glutamate (0.1-10 nmol) produced a dose-dependent increase in arterial pressure and heart rate. Pretreatment with CARTp dose-dependently potentiated the pressor effects of glutamate (1 nmol), which by itself elicited a moderate increase of blood pressure and heart rate. Further, CARTp significantly potentiated the tachycardic effect of glutamate at 1 and 5 nmol, but attenuated the response at 10 nmol. The effect of CARTp was long-lasting, as it enhanced glutamatergic responses up to 90 min after administration. Prior injection of CARTp antiserum (1:500) but not normal rabbit serum nullified the potentiating effect of CARTp on glutamatergic responses. The result suggests that CARTp, whose immunoreactivity is detectable in sympathetic preganglionic neurons as well as in fibers projecting into the intermediolateral cell column, augments spinal sympathetic outflow elicited by glutamate at lower concentrations and may directly excite neurons in the intermediolateral cell column at higher concentrations.
Scruggs
Phouangmala
P
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, P.O. Box 70577, Johnson City, TN 37614, USA.
Lai
Chih C
CC
Scruggs
Jesse E
JE
Dun
Nae J
NJ
D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D018698:Glutamic Acid