Effects of tachykinins on rapidly adapting pulmonary stretch receptors and total lung resistance in anesthetized, artificially ventilated rabbits.
In anesthetized, artificially ventilated rabbits not treated with thiorphan (2 mg/kg), a neutral endopeptidase (NEP) inhibitor, substance P (SP) and neurokinin A (NKA) in doses from 0.2 to 2.7 microg/kg produced dose-related increases in rapidly adapting pulmonary stretch receptor (RAR) activity without any significant changes in total lung resistance (RL), whereas neurokinin B (NKB) at the same concentrations did not significantly alter either RAR activity or RL. In comparison with the excitatory responses of RAR activity to SP and NKA, the magnitudes of increased receptor activity evoked SP were significantly larger than those after NKA administration. The rank order of tachykinins for RAR stimulus potency was SP > NKA > KB. Pretreatment with thiorphan potentiated the increases of RAR activity and RL induced by SP but had no effect on the RAR and RL responses to NKA and NKB. Subsequent administration of L 659, 877 (a selective NK2 receptor antagonist, 2. 3 and 7.6 microg/kg) that dose-dependently inhibited NKA-induced RAR stimulation did not significantly influence augmentation of the RAR and RL responses to SP. Administration of atropine (2 mg/kg, n = 6) in thiorphan-treated rabbits, which had no effect on NKA- and NKB-induced RAR stimuli, significantly attenuated the increases of RAR activity and RL induced by SP. These results suggest that tachykinin-induced RAR stimulation is mediated by the activation of NK2 receptors, probably involving participation of NK1 receptors. Furthermore, potentiation of the increases of RAR activity and RL produced by SP administration in the presence of thiorphan is partly mediated by facilitation of cholinergic neurotransmission.
Matsumoto
S
S
Department of Physiology, Nippon Dental University, Tokyo, Japan.
Takeda
M
M
Saiki
C
C
Takahashi
T
T
Ojima
K
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D012121:Respiration, Artificial; D015320:Tachykinins / Q000494:pharmacology*; D015244:Thiorphan / Q000494:pharmacology
D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); D001285:Atropine; D015244:Thiorphan