Effects of substance P on neuronal firing of pallidal neurons in parkinsonian rats.
Substance P is an important neurotransmitter or neuromodulator in central nervous system. Morphological studies have revealed the existence of substance P and its high affinity receptor, neurokinin-1 receptor, in globus pallidus. The expression of neurokinin-1 receptor in external globus pallidus has been reported to be decreased or unchanged in parkinsonian patients. To further investigate the effects of pallidal neurokinin-1 receptor in Parkinson's disease, an in vivo extracellular recording in 6-hydroxydopamine parkinsonian rats was performed. Micro-pressure ejection of selective neurokinin-1 receptor agonist, [Sar9,Met(O2)11] substance P (0.1mM), increased the spontaneous firing rate of pallidal neurons by 9.1% on the lesioned side, which was significantly weaker than that on the unlesioned side (20.7%), and that in normal rats (30.0%). The selective neurokinin-1 receptor antagonist, SR140333B, prevented the excitatory effects induced by [Sar9,Met(O2)11] substance P. Based on the action of substance P in globus pallidus of parkinsonian rats we hypothesize that the activity of neurokinin-1 receptors in globus pallidus may be decreased under parkinsonian state. This finding may provide a rationale for further investigations into the potential of pallidal substance P system in the treatment of Parkinson's disease.
Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao, 266071 Shandong, China.
Qiao-Ling
QL
Cui
Wing-Ho
WH
Yung
Lei
L
Chen
D000200:Action Potentials / Q000187:drug effects*; D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003192:Compulsive Behavior / Q000139:chemically induced / Q000503:physiopathology; D004195:Disease Models, Animal; D004347:Drug Interactions; D005917:Globus Pallidus / Q000473:pathology*; D008297:Male; D008474:Medial Forebrain Bundle / Q000293:injuries / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology
D018663:Adrenergic Agents; C526005:SR140333B; D014326:Tropanes; D013373:Substance P; D016627:Oxidopamine