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

Abstract

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.

Figure 1

Respiratory response to microinjection of capsaicin (1 nmol) into the commissural nucleus of the solitary tract of urethane-anaesthetized, spontaneously breathing adult rats (10 weeks) pretreated as neonates (day 2) with capsaicin (50 mg kg⁻¹ s.c.). (a) Tidal volume (VT), (b) respiratory frequency (f) and (c) minute ventilation (VE). Values are the mean of four animals and vertical bars show s.e.mean. Where error bars are not obvious, they are within the symbol.

Figure 2

Respiratory response to microinjection of tachykinins into the commissural nucleus of the solitary tract of urethane-anaesthetized, spontaneously breathing adult rats (10 weeks) pretreated as neonates (day 2) with capsaicin (50 mg kg⁻¹ s.c.). Doses injected were 33 pmol SP (a–c), 10 pmol NKA (d–f) and 100 pmol NKB (g–i). Tidal volume (VT), respiratory frequency (f) and minute ventilation (VE). Values are the mean of four animals and vertical bars show s.e.mean. Where error bars are not obvious, they are within the symbol.

Figure 3

Respiratory response to microinjection of NK₁ and NK₃ receptor-selective tachykinins into the commissural nucleus of the solitary tract of urethane-anaesthetized, spontaneously breathing adult rats (10 weeks) pretreated as neonates (day 2) with capsaicin (50 mg kg⁻¹ s.c.). Doses injected were 33 pmol [Sar⁹,Met(O₂)¹¹]-SP (a–c), 10 pmol septide (d–f) and 10 pmol senktide (g–i). Tidal volume (VT), respiratory frequency (f) and minute ventilation (VE). Values are the mean of four animals and vertical bars show s.e.mean. Where error bars are not obvious, they are within the symbol.

Figure 4

Respiratory response to microinjection of 300 pmol of the NK₂ receptor-selective agonist, [Nle¹⁰]-NKA(4-10) into the commissural nucleus of the solitary tract of urethane-anaesthetized, spontaneously breathing adult rats (10 weeks) pretreated as neonates (day 2) with capsaicin (50 mg kg⁻¹ s.c.). (a) Tidal volume (VT), (b) respiratory frequency and (c) minute ventilation (VE). Values are the mean of four animals and vertical bars show s.e.mean. Where error bars are not obvious, they are within the symbol.