Preferential synaptic relationships between substance P-immunoreactive boutons and neurokinin 1 receptor sites in the rat spinal cord.
Substance P plays an important role in the transmission of pain-related information in the dorsal horn of the spinal cord. Recent immunocytochemical studies have shown a mismatch between the distribution of substance P and its receptor in the superficial laminae of the dorsal horn. Because such a mismatch was not observed by using classical radioligand binding studies, we decided to investigate further the issue of the relationship between substance P and its receptor by using an antibody raised against a portion of the carboxyl terminal of the neurokinin 1 receptor and a bispecific monoclonal antibodies against substance P and horseradish peroxidase. Light microscopy revealed a good correlation between the distributions of substance P and the neurokinin 1 receptor, both being localized with highest densities in lamina I and outer lamina II of the spinal dorsal horn. An ultrastructural double-labeling study, combining preembedding immunogold with enzyme-based immunocytochemistry, showed that most neurokinin 1 receptor immunoreactive dendrites were apposed by substance P containing boutons. A detailed quantitative analysis revealed that neurokinin 1 receptor immunoreactive dendrites received more appositions and synapses from substance P immunoreactive terminals than those not expressing the neurokinin 1 receptor. Such preferential innervation by substance P occurred in all superficial dorsal horn laminae even though neurokinin 1 receptor immunoreactive dendrites were a minority of the total number of dendritic profiles in the above laminae. These results suggest that, contrary to the belief that neuropeptides act in a diffuse manner at a considerable distance from their sites of release, substance P should act on profiles expressing the neurokinin 1 receptor at a short distance from its site of release.
McLeod
A L
AL
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Krause
J E
JE
Cuello
A C
AC
Ribeiro-da-Silva
A
A
D000344:Afferent Pathways; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013373:Substance P / Q000032:analysis / Q000502:physiology*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013788:Thalamus / Q000502:physiology
D018040:Receptors, Neurokinin-1; D013373:Substance P