Respiratory actions of tachykinins in the nucleus of the solitary tract: effect of neonatal capsaicin pretreatment

Br J Pharmacol. 2000 Mar;129(6):1132-9. doi: 10.1038/sj.bjp.0703173.


1. The respiratory response to microinjection of capsaicin and tachykinin receptor agonists into the commissural nucleus of the solitary tract (cNTS) was investigated in adult, urethane-anaesthetized rats which had been pretreated with capsaicin (50 mg kg(-1) s.c.) or vehicle (10% Tween 80, 10% ethanol in saline) as day 2 neonates. 2. Microinjection of capsaicin (1 nmol) into the cNTS of vehicle-pretreated rats, significantly reduced respiratory frequency (59 breaths min(-1), preinjection control, 106 breaths min(-1)) without affecting tidal volume (VT). In capsaicin-pretreated rats, the capsaicin-induced bradypnoea was markedly attenuated (minimum frequency, 88 breaths min(-1); control, 106 breaths min(-1)). 3. In vehicle-pretreated rats, microinjection of substance P (SP, 33 pmol), neurokinin A (NKA, 33 pmol) and NKB (330 pmol), and the selective NK(1) tachykinin receptor agonists, [Sar(9), Met(O(2))(11)]-SP (33 pmol) and septide (10 pmol), increased VT (maxima, 3.60 - 3.93 ml kg(-1)) compared with preinjection control (2.82 ml kg(-1)), without affecting frequency. The selective NK(3) agonist senktide (10 pmol) also increased VT (3.93 ml kg(-1)) which was accompanied by a bradypnoea (-25 breaths min(-1)). The selective NK(2) agonist, [Nle(10)]-NKA(4-10) (330 pmol) increased VT slightly but significantly decreased frequency (-12 breaths min(-1)). In capsaicin-pretreated rats, VT responses to SP and [Sar(9), Met(O(2))(11)]-SP were increased whereas the response to septide was abolished. Both the VT and bradypnoeic responses to senktide and [Nle(10)]-NKA(4-10) were significantly enhanced. 4. These results show that neonatal capsaicin administration markedly reduces the respiratory response to microinjection of capsaicin into the cNTS. The destruction of capsaicin-sensitive afferents appears to sensitize the NTS to SP, NKB, [Sar(9),Met(O(2))(11)]-SP, senktide and [Nle(10)]-NKA(4-10). Moreover, the loss of septide responsiveness in capsaicin-pretreated rats, suggests that 'septide-sensitive' NK(1) receptors may be located on the central terminals of afferent neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / physiology*
  • Capsaicin / pharmacology*
  • Male
  • Microinjections
  • Neurokinin A / administration & dosage
  • Neurokinin A / pharmacology
  • Neurokinin B / administration & dosage
  • Neurokinin B / pharmacology
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Wistar
  • Respiratory Mechanics / drug effects*
  • Solitary Nucleus / drug effects*
  • Substance P / analogs & derivatives
  • Substance P / pharmacology
  • Tachykinins / pharmacology*


  • Peptide Fragments
  • Tachykinins
  • senktide
  • Substance P
  • Neurokinin A
  • Neurokinin B
  • Capsaicin