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Respiratory actions of tachykinins in the nucleus of the solitary tract: effect of neonatal capsaicin pretreatment
journal contribution
posted on 2023-05-16, 12:08 authored by Mazzone, SB, Dominic GeraghtyDominic Geraghty1. 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.
History
Publication title
British Journal of PharmacologyVolume
129Issue
6Pagination
1132-1139ISSN
0007-1188Department/School
School of Health SciencesPublisher
Nature Publishing CompanyPlace of publication
United KingdomRepository Status
- Restricted