Characterization and regulation of neurokinin1, receptors in primary cultures of rat neonatal spinal neurons

Virginia S Seybold, L. G. Abrahams

Research output: Contribution to journalLetter

11 Scopus citations

Abstract

Neurokinin1 receptors are the primary target of substance P released from neurons during neural transmission, yet little is known regarding the regulation of neurokinin1 receptors on neurons.125I-Bolton-Hunter-substance P was used in the present studies to determine whether primary cultures of rat neonatal spinal cord express neurokinin1 receptors and, therefore, can be used as a model to regulation of neuronal neurokinin receptors.125I-Bolton-Hunter-substance P bound to a single site in neuron-enriched cultures with an affinity of 256 nM, which is comparable to its high affinity binding on adult rat spinal cord. Treatment of neuron-enriched cultures with 10 nM substance P resulted in a 47% decrease in125I-Bolton-Hunter-substance P binding at 24h which was due to a decrease in affinity of the receptor. However, at 48 h after treatment with substance P,125I-Bolton-Hunter-substance P binding increased by 44%. The increase in binding was due to a two-fold increase in receptor density. These changes occurred in the presence of 0.5 μ M tetrodotoxin, decreasing the likelihood that the changes in binding were secondary to the release of transmitters by substance P. Furthermore, substance P1-7, a metabolite of substance P that hm putative physiological effects, did not alter125I-Bolton-Hunter-substance P binding. These data provide evidence that neuronal neurokinin1 receptors are under homologous regulation in primary cultures of neonatai rat spinal cord and suggest that a similar mechanism occurs in vivo. Furthermore, the data suggest that a decrease in affinity of the neurokinin1 receptor may contribute, in part, to tachyphylaxis to substance P.

Original languageEnglish (US)
Pages (from-to)1263-1273
Number of pages11
JournalNeuroscience
Volume69
Issue number4
DOIs
StatePublished - Dec 1995

Keywords

  • spinal cord
  • substance P
  • substance P

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