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Respiratory actions of tachykinins in the nucleus of the solitary tract: effect of neonatal capsaicin pretreatment
Author(s) -
Mazzone Stuart B,
Geraghty Dominic P
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703173
Subject(s) - capsaicin , substance p , microinjection , neurokinin a , agonist , endocrinology , chemistry , medicine , solitary tract , neurokinin b , respiratory rate , respiratory system , anesthesia , receptor , neuropeptide , heart rate , blood pressure
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. 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 (V T ). In capsaicin‐pretreated rats, the capsaicin‐induced bradypnoea was markedly attenuated (minimum frequency, 88 breaths min −1 ; control, 106 breaths min −1 ). 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 V T (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 V T (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 V T slightly but significantly decreased frequency (−12 breaths min −1 ). In capsaicin‐pretreated rats, V T responses to SP and [Sar 9 ,Met(O 2 ) 11 ]‐SP were increased whereas the response to septide was abolished. Both the V T and bradypnoeic responses to senktide and [Nle 10 ]‐NKA(4‐10) were significantly enhanced. 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.British Journal of Pharmacology (2000) 129 , 1132–1139; doi: 10.1038/sj.bjp.0703173