Contractile effects of neuropeptide Y in human subcutaneous resistance arteries are mediated by Y1 receptors

Journal of Cardiovascular Pharmacology
T NilssonL Edvinsson

Abstract

The aim of our study was to determine the neuropeptide Y (NPY) receptor subtype responsible for the NPY-induced contraction of human subcutaneous (s.c.) resistance arteries. To elucidate this, we used (a) in vitro studies of NPY agonists: NPY, peptide YY (PYY), and Pro34NPY induced equally strong and equipotent concentration-dependent contractions of human s.c. resistance arteries, whereas NPY13-36 and NPY18-36 had no contractile effects; (b) in vitro studies using the NPY Y1-receptor antagonist, BIBP3226, which in nanomolar concentrations inhibited the contractile effect of NPY, causing a rightward shift of the concentration-response curve. pEC50 for NPY alone, 8.41 +/- 0.21; NPY + BIBP3226, 10 nM, 7.79 +/- 0.21; NPY + BIBP3226, 100 nM, 7.18 +/- 0.18; NPY + BIBP3226, 1 microM, 6.32 +/- 0.05 (n = 5-8). Schild-plot analysis indicated competitive antagonism: pA2 = 8.53 +/- 0.22 and slope = 0.99 +/- 0.14; (c) with reverse transcriptase-polymerase chain reaction (RT-PCR), we detected messenger RNA (mRNA) encoding the human NPY Y1 receptor and a splice variant of the receptor in human s.c. resistance arteries. On the basis of the agonists' potency order, the antagonistic effect of BIBP3226 on the NPY-induced contraction, and the pre...Continue Reading

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Citations

Jul 21, 1998·European Journal of Pharmacology·A Franco-Cereceda, J Liska
Dec 16, 1998·European Journal of Pharmacology·A BergdahlL Edvinsson
Jul 3, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Gary J HodgesJ Kevin Shoemaker
Jul 13, 2002·The Journal of Comparative Neurology·Hideki MatsudaTomas Hökfelt
Aug 14, 2008·International Endodontic Journal·I A El KarimF T Lundy
Mar 16, 2017·Experimental Physiology·James A LangKevin A Smaller
Feb 12, 1998·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·M Jackerott, L I Larsson
Oct 20, 1999·The Annals of Otology, Rhinology, and Laryngology·R UddmanL Edvinnsson
Dec 4, 2004·American Journal of Physiology. Heart and Circulatory Physiology·John M JohnsonWojciech A Kosiba
Mar 15, 2001·American Journal of Physiology. Heart and Circulatory Physiology·D P StephensJ M Johnson
Apr 25, 2003·Canadian Journal of Physiology and Pharmacology·Jennifer PonsZofia Zukowska
May 29, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Dan P StephensJohn M Johnson

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