The actions of receptor-selective substance P analogs on myenteric neurons: an electrophysiological investigation

Menachem Hanani*, Michael Chorev, Chaim Gilon, Zvi Selinger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Intracellular recordings were made from myenteric neurons of the guinea-pig duodenum and the responses to local ejection of several substance P (SP) analogs were examined. It was found that senktide (succinyl-[Asp6,Me-Phe8]SP-(6-11), a selective analog for the NK-3 (SP-N) receptor, was particularly effective in depolarizing the neurons. It was 20-100 times more potent than SP and about 1000-fold more potent than the selective analogs for the NK-1 (SP-P) receptor, which resides on muscle cells. The response to the peptides was prolonged (20-120 s), but in about 20% of the cells there was a fast, early depolarizing component (observed only with senktide). In most cases there was an increase in the input resistance of the cell during the slow depolarization. Together with the finding that the response reversed at about -90 mV, this indicates that the response is due to the closure of K+ channels. The results support the existence of an NK-3 (SP-N) receptor and provide direct information about the membrane mechanisms through which NK-3 agonists excite myenteric neurons.

Original languageEnglish
Pages (from-to)247-253
Number of pages7
JournalEuropean Journal of Pharmacology
Volume153
Issue number2-3
DOIs
StatePublished - 24 Aug 1988

Keywords

  • Myenteric plexus
  • Senktide
  • Substance P
  • Substance P analogs
  • Tachykinins

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