Chronic non-peptide neurokinin receptor antagonist treatment alters striatal tachykinin peptide and receptor gene expression in the rat.
The neurokinin-1 receptor (NK-1R) and the tachykinin peptide substance P (SP) are found throughout the central nervous system (CNS) and are involved in the regulation of sensory, cardiovascular, and inflammatory function. Selective antagonists for the NK-1R such as CP-122,721 block NK-1R-mediated responses both in vitro and in vivo. This study investigated the effects of long-term daily CP-122,721 treatment on gene expression of SP and the NK-1R in the striatum and hindbrain of the rat. The striatum and hindbrain of rats receiving CP122,721 (5, 30, or 150 mg/kg) once-daily for 30 days were assayed for SP- and NK-1R-encoding mRNAs using solution hybridization-nuclease protection assays. Results show that treatment with CP-122,721 significantly increased SP-encoding mRNA and NK-1R mRNA levels in the striatum, but not in the hindbrain. The ability of CP-122,721 to alter SP and NK-1R gene expression may provide a use for non-peptide neurokinin receptor antagonists in the modulation of systems regulated by NK-1R function.
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA. kmccarso@kumc.edu
K E
KE
McCarson
J E
JE
Krause
S
S
McLean
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000235:genetics; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C099414:(2S,3S)-2-phenyl-3-((5-trifluoromethoxy-2-methoxy)benzylamino)piperidine