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Respiratory actions of tachykinins in the nucleus of the solitary tract: characterization of receptors using selective agonists and antagonists
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.0703172
Subject(s) - neurokinin b , neurokinin a , substance p , endocrinology , medicine , agonist , tachykinin receptor , stimulation , solitary tract , microinjection , receptor , biology , chemistry , neuropeptide
The respiratory response to microinjection of tachykinins and analogues into the commissural nucleus of the solitary tract (cNTS) of urethane‐anaesthetized rats was investigated in the presence and absence of selective tachykinin NK 1 , NK 2 and NK 3 antagonists (RP 67580, SR 48968 and SR 142801, respectively). All tachykinins, except for the selective NK 2 agonist, [Nle 10 ]‐NKA(4‐10), increased tidal volume (V T ). The rank potency order of naturally‐occurring tachykinins was neurokinin A (NKA)substance P (SP)>>NKB, whereas the rank order for selective analogues was senktideseptide>> [Sar 9 ,Met(O 2 ) 11 ]‐SP>>[Nle 10 ]‐NKA(4‐10). Septide (NK 1 ‐selective) and senktide (NK 3 ‐selective) were 22 fold more potent (pD 2 ∼12) at stimulating V T than SP (pD 2 ∼10.5). Tachykinin agonists produced varying degrees of respiratory slowing, independent of changes in V T . At doses producing maximum stimulation of V T , agonists induced either a mild (<10 breaths min −1 decrease; SP and septide), moderate (10–25 breaths min −1 decrease; NKA, NKB and [Sar 9 ,Met(O 2 ]‐SP) or severe (∼40 breaths min −1 decrease; senktide) bradypnoea. [Nle 10 ]‐NKA(4‐10) produced a dose‐dependent bradypnoea without affecting V T . RP 67580 significantly attenuated the V T response to SP (33 pmol) and NKA (10 pmol) but not NKB (100 pmol). In the presence of RP 67580, the mild bradypnoeic response to NKB was significantly enhanced whereas SP and NKA induced a bradypnoea which was not observed in the absence of RP 67580. SR 48968 had no effect on the V T response to SP or NKB, markedly enhanced the V T response to NKA and completely blocked the bradypnoeic response to [Nle 10 ]‐NKA(4‐10). Only SR142801 attenuated the V T response to NKB. The present data suggest that all three tachykinin receptors (NK 1 , NK 2 and NK 3 ) are present in the cNTS and are involved in the central control of respiration.British Journal of Pharmacology (2000) 129 , 1121–1131; doi: 10.1038/sj.bjp.0703172