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. 1996 Aug;118(8):2079–2084. doi: 10.1111/j.1476-5381.1996.tb15647.x

Intranasal administration of neuropeptide Y in man: systemic absorption and functional effects.

J S Lacroix 1, A P Ricchetti 1, D Morel 1, B Mossimann 1, B Waeber 1, E Grouzmann 1
PMCID: PMC1909896  PMID: 8864546

Abstract

1. Exogenous neuropeptide Y (NPY, 10 nmol, 50 nmol and 100 nmol) and its vehicle (NaCl 0.9%) were administered in a double blind, randomized and controlled manner by intranasal spray in 7 healthy volunteers. Variations of plasma NPY concentration over time were measured during 120 min. Forty min after the administration of 50 nmol and 100 nmol of exogenous NPY, plasma NPY increased from 5.5 +/- 1.1 pM to 9.8 +/- 2.3 pM (P < 0.05) and from 9.06 +/- 5.1 pM to 20.8 +/- 6.16 pM (P < 0.001), respectively. There was no significant modification of the mean arterial blood pressure and no subjective discomfort was reported. 2. Nasal airway resistance (NAR) was measured by anterior rhinomanometry and was reduced by 25 +/- 3% and 32 +/- 5% after the spray of 50 nmol and 100 nmol, respectively, for about 90 min. 3. Double-blind, randomized, placebo-controlled and 3-way crossover design experiments were performed in 8 healthy volunteers to evaluate the influence of intranasal pretreatment with NPY (20 nmol) and the mixed alpha 1/alpha 2-adrenoceptor agonist oxymetazoline (20 nmol) on the functional effects of subsequent local irritation evoked by capsaicin (3.3 x 10(-4) mol). Subjective evaluation of NAR and local intensity of discomfort were evaluated by means of a visual analogue scale. Nasal secretions were collected and objective NAR was recorded by rhinomanometry. 4. Subjective NAR, nasal secretions and rhinomanometry recordings were not modified by intranasal application of saline, NPY or oxymetazoline. Subjective nasal obstruction, local discomfort, nasal secretions and NAR increase evoked by capsaicin were markedly reduced by NPY pretreatment (P < 0.05) when compared to saline or oxymetazoline. 5. It is concluded that intranasal application of exogenous NPY has very low systemic absorption but induced long lasting nasal vasoconstriction without cardiovascular effects. Pretreatment of the nasal mucosa with exogenous NPY reduces both secretagogue and vasodilator responses to subsequent application of capsaicin.

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Selected References

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  1. Baraniuk J. N., Castellino S., Lundgren J. D., Goff J., Mullol J., Merida M., Shelhamer J. H., Kaliner M. A. Neuropeptide Y (NPY) in human nasal mucosa. Am J Respir Cell Mol Biol. 1990 Aug;3(2):165–173. doi: 10.1165/ajrcmb/3.2.165. [DOI] [PubMed] [Google Scholar]
  2. Baraniuk J. N., Silver P. B., Kaliner M. A., Barnes P. J. Neuropeptide Y is a vasoconstrictor in human nasal mucosa. J Appl Physiol (1985) 1992 Nov;73(5):1867–1872. doi: 10.1152/jappl.1992.73.5.1867. [DOI] [PubMed] [Google Scholar]
  3. Konno A., Togawa K. Role of the vidian nerve in nasal allergy. Ann Otol Rhinol Laryngol. 1979 Mar-Apr;88(2 Pt 1):258–266. doi: 10.1177/000348947908800219. [DOI] [PubMed] [Google Scholar]
  4. Lacroix J. S. Adrenergic and non-adrenergic mechanisms in sympathetic vascular control of the nasal mucosa. Acta Physiol Scand Suppl. 1989;581:1–63. [PubMed] [Google Scholar]
  5. Lacroix J. S., Anggård A., Hökfelt T., O'Hare M. M., Fahrenkrug J., Lundberg J. M. Neuropeptide Y: presence in sympathetic and parasympathetic innervation of the nasal mucosa. Cell Tissue Res. 1990 Jan;259(1):119–128. doi: 10.1007/BF00571436. [DOI] [PubMed] [Google Scholar]
  6. Lacroix J. S., Kurt A. M., Pochon N., Bretton C., Lundberg J. M., Deshusses J. Neutral endopeptidase activity and concentration of sensory neuropeptide in the human nasal mucosa. Eur Arch Otorhinolaryngol. 1995;252(8):465–468. doi: 10.1007/BF02114752. [DOI] [PubMed] [Google Scholar]
  7. Lacroix J. S., Ulman L. G., Potter E. K. Modulation by neuropeptide Y of parasympathetic nerve-evoked nasal vasodilatation via Y2 prejunctional receptor. Br J Pharmacol. 1994 Oct;113(2):479–484. doi: 10.1111/j.1476-5381.1994.tb17014.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lundberg J. M., Terenius L., Hökfelt T., Martling C. R., Tatemoto K., Mutt V., Polak J., Bloom S., Goldstein M. Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand. 1982 Dec;116(4):477–480. doi: 10.1111/j.1748-1716.1982.tb07171.x. [DOI] [PubMed] [Google Scholar]
  9. Lundblad L., Saria A., Lundberg J. M., Anggård A. Increased vascular permeability in rat nasal mucosa induced by substance P and stimulation of capsaicin-sensitive trigeminal neurons. Acta Otolaryngol. 1983 Nov-Dec;96(5-6):479–484. doi: 10.3109/00016488309132734. [DOI] [PubMed] [Google Scholar]
  10. Matran R., Martling C. R., Lundberg J. M. Inhibition of cholinergic and non-adrenergic, non-cholinergic bronchoconstriction in the guinea pig mediated by neuropeptide Y and alpha 2-adrenoceptors and opiate receptors. Eur J Pharmacol. 1989 Apr 12;163(1):15–23. doi: 10.1016/0014-2999(89)90390-7. [DOI] [PubMed] [Google Scholar]
  11. Nuki C., Kawasaki H., Takasaki K. Effect of neuropeptide Y on vasodilation mediated by calcitonin gene-related peptide (CGRP)-containing nerves in the mesenteric resistance vessel of the rat. Jpn J Pharmacol. 1990 May;53(1):125–128. doi: 10.1254/jjp.53.125. [DOI] [PubMed] [Google Scholar]
  12. Pernow J. Co-release and functional interactions of neuropeptide Y and noradrenaline in peripheral sympathetic vascular control. Acta Physiol Scand Suppl. 1988;568:1–56. [PubMed] [Google Scholar]
  13. Petersson G., McCaffrey T. V., Malm L. Substance P and nasal secretion in dog, rat, and man. Ann Allergy. 1989 May;62(5):410–414. [PubMed] [Google Scholar]
  14. Potter E. K. Prolonged non-adrenergic inhibition of cardiac vagal action following sympathetic stimulation: neuromodulation by neuropeptide Y? Neurosci Lett. 1985 Mar 15;54(2-3):117–121. doi: 10.1016/s0304-3940(85)80065-3. [DOI] [PubMed] [Google Scholar]
  15. Proud D., Togias A., Naclerio R. M., Crush S. A., Norman P. S., Lichtenstein L. M. Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen. J Clin Invest. 1983 Nov;72(5):1678–1685. doi: 10.1172/JCI111127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Secher C., Kirkegaard J., Borum P., Maansson A., Osterhammel P., Mygind N. Significance of H1 and H2 receptors in the human nose: rationale for topical use of combined antihistamine preparations. J Allergy Clin Immunol. 1982 Sep;70(3):211–218. doi: 10.1016/0091-6749(82)90044-6. [DOI] [PubMed] [Google Scholar]
  17. Stjärne P., Lacroix J. S., Anggård A., Lundberg J. M. Compartment analysis of vascular effects of neuropeptides and capsaicin in the pig nasal mucosa. Acta Physiol Scand. 1991 Mar;141(3):335–342. doi: 10.1111/j.1748-1716.1991.tb09089.x. [DOI] [PubMed] [Google Scholar]
  18. Stretton C. D., Barnes P. J. Modulation of cholinergic neurotransmission in guinea-pig trachea by neuropeptide Y. Br J Pharmacol. 1988 Mar;93(3):672–678. doi: 10.1111/j.1476-5381.1988.tb10325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wahlestedt C., Yanaihara N., Håkanson R. Evidence for different pre-and post-junctional receptors for neuropeptide Y and related peptides. Regul Pept. 1986 Feb;13(3-4):307–318. doi: 10.1016/0167-0115(86)90048-0. [DOI] [PubMed] [Google Scholar]
  20. Warner M. R., Levy M. N. Neuropeptide Y as a putative modulator of the vagal effects on heart rate. Circ Res. 1989 May;64(5):882–889. doi: 10.1161/01.res.64.5.882. [DOI] [PubMed] [Google Scholar]

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