Respiratory actions of tachykinins in the nucleus of the solitary tract: effect of neonatal capsaicin pretreatment
Mazzone, SB and Geraghty, DP, Respiratory actions of tachykinins in the nucleus of the solitary tract: effect of neonatal capsaicin pretreatment, British Journal of Pharmacology, 129, (6) pp. 1132-1139. ISSN 0007-1188 (2000) [Refereed Article]
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 capsaiein (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 [NIe 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.