Tachykinins activate guinea-pig alveolar macrophages: involvement of NK2 and NK1 receptors.
1. The effects of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were evaluated on superoxide anion (O2-.) production by guinea-pig alveolar macrophages (AM). 2. SP dose-dependently (ED50 = 0.7 nM) evoked O2-. production from guinea-pig AM; the N-terminal heptapeptide, SP(1-7), was ineffective. In the presence of thiorphan (10(-5) M), an enkephalinase inhibitor, the stimulating effects of SP were not significantly modified. NKA and NKB were both able to induce O2-. production from guinea-pig AM, ED50 values being 0.1 and 1.3 nM, respectively. Therefore, the rank order of activity of natural tachykinins was NKA greater than SP greater than NKB. Tachykinin-evoked effects were quantitatively similar to those elicited by the autacoid mediator PAF-acether and less than those induced by the synthetic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). 3. The NK2 receptor agonist [beta-Ala8]-NKA (4-10) dose-dependently evoked O2-. production from guinea-pig AM; the NK1 receptor agonist [Pro9]-SP sulphone acted only at high concentrations, while the NK3 receptor agonist [Me,Phe7]-NKB was ineffective. 4. These findings indicate that guinea-pig AM possess NK2 and possibly some NK1 tachykinin receptors and further suggest tachykinin involvement in lung pathophysiology.
Brunelleschi
S
S
Department of Pharmacology, Univ. Florence, Italy.
Vanni
L
L
Ledda
F
F
Giotti
A
A
Maggi
C A
CA
Fantozzi
R
R
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D015320:Tachykinins / Q000494:pharmacology*
D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D013481:Superoxides; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015288:Neurokinin A; D015287:Neurokinin B