These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Characterization of NK1 and NK2 tachykinin receptors in guinea-pig and rat bronchopulmonary and vascular systems.
    Author: Floch A, Fardin V, Cavero I.
    Journal: Br J Pharmacol; 1994 Mar; 111(3):759-68. PubMed ID: 7517328.
    Abstract:
    1. NK1 and NK2 tachykinin receptors were characterized in guinea-pig and rat bronchopulmonary systems and in the vasculature of the rat by use of radioligand binding and/or functional studies. 2. The radioligands for NK1 and NK2 receptors ([3H]-SP and [3H]-pNKA, respectively) did not label tachykinin receptors in homogenates of rat lungs or bronchi. In contrast, in the guinea-pig, [3H]-SP bound with high affinity to these tissues (KD = 0.23 +/- 0.08 nM and 0.34 +/- 0.05 nM, for lungs and bronchi, respectively). The total number of binding sites was 4.6 fold greater in bronchus (Bmax = 135 +/- 27 fmol mg-1 protein) than in lung homogenates (Bmax = 29.3 +/- 0.1 fmol mg-1 protein). Furthermore, this binding was markedly displaced by CP-96,345 (pKi = 9.5 +/- 0.1) and RP 67580 (pKi = 7.6 +/- 0.1), antagonists of NK1 receptors, slightly displaced by SR 48968 (pKi = 6.6 +/- 0.1), but not affected by actinomycin D or L-659,877, antagonists of NK2 receptors. Specific binding of [3H]-pNKA, detected in guinea-pig bronchi (KD = 5.2 +/- 0.1 nM, and Bmax = 203 +/- 19 fmol mg-1 protein) but not in lungs, was similarly (40 to 53%) displaced by RP 67580 (1 microM), CP-96,345 (10 and 100 nM) or SR 48968 (10 and 100 nM). The displacement approximately doubled (87 to 91%) when SR 48968 (10 nM) was combined with either RP 67580 (1 microM) or CP-96,345 (10 nM), but not when RP 67580 was combined with CP-96,345. 3. In urethane-anaesthetized guinea-pigs, i.v. injections of the NK1 receptor agonists SP, [Pro9]-SP, [Sar9,Met(O2)11]-SP and septide, as well as the NK2 receptor agonists NKA and [Lys5,MeLeu9,NLeu10]-NKA(4-10) (0.1-10 micrograms kg-1, i.v.), dose-dependently increased lung inflation pressure. The most potent of these peptides were septide and [Lys5, MeLeu9,NLeu10]-NKA(4-10) (EC50 = 0.38 +/- 0.07 and 0.07 +/- 0.02 microgram kg-1, respectively). Interestingly, septide was 130 fold less potent than SP in displacing [3H]-SP from its binding sites in the guinea-pig lung, whereas it was 14 fold more potent than SP as a bronchoconstrictor. RP 67580 (0.3-5 mg kg-1, i.v.) and CP-96,345 (0.01-3 mg kg-1, i.v.) dose-dependently reduced the bronchoconstriction produced by the NK1 receptor agonists. Conversely, the NK2 receptor antagonists actinomycin D (1-10 mg kg-1, i.v.) and SR 48968 (0.03-0.3 mg kg-1, i.v.) inhibited specifically the responses induced by NK2 receptor agonists.4. In pentobarbitone-anaesthetized rats, the NK1 and NK2 receptor agonists (0.01-4 microg kg-1, i.v.)produced dose-dependent hypotensive responses. The order of potency was SP = [Sar9, Met(0211]-SP = [Pro9]-SP > septide = NKA >[Lys5, MeLeu9, NLeu 10-NKA.(4-10). RP 67580 (0.13-0.5 mg kg-1,i.v.) and CP-96,345 (0.5-2 mg kg-1, i.v.) antagonized in a dose-related manner (20 to 64%) the vascular effects of both NK, and NK2 receptor agonists, whereas actinomycin D (3 mg kg-1, i.v.) and SR 48968(2 mg kg-1, i.v.) did not. RP 67580 was approximately 4 times more potent than CP-96,345.5. These studies indicate that NK1 and NK2 receptors are both present in the guinea-pig bronchopulmonary system whereas only NK1 receptors are detectable in the rat vasculature under our experimental conditions. Furthermore, NK1 receptors in the guinea-pig bronchopulmonary system are pharmacologically distinct from those present in the rat vascular system, since both agonist potencies and antagonist affinities differ between the two species.
    [Abstract] [Full Text] [Related] [New Search]