Characterization and molecular cloning of vascular neuropeptide Y receptor subtypes in pig and dog
| Autor: | A. Jonas Ekstrand, Carina Nihlen, Rickard E. Malmström, Jan M. Lundberg, Jan-Arne Björkman, Mona Byström, Tomas Hökfelt |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Agonist
medicine.medical_specialty DNA Complementary Swine Physiology medicine.drug_class Molecular Sequence Data Clinical Biochemistry Spleen Biology Arginine Kidney Biochemistry Cellular and Molecular Neuroscience Dogs Endocrinology Species Specificity Internal medicine medicine Animals Humans Peptide YY Amino Acid Sequence RNA Messenger Cloning Molecular Receptor In Situ Hybridization DNA Primers BIBP-3226 Base Sequence Sequence Homology Amino Acid Reverse Transcriptase Polymerase Chain Reaction Neuropeptide Y receptor Receptor antagonist Receptors Neuropeptide Y medicine.anatomical_structure Vasoconstriction medicine.symptom |
| Zdroj: | Regulatory Peptides. :55-70 |
| ISSN: | 0167-0115 |
| Popis: | Cloning with subsequent in vitro and in vivo characterization of vascular neuropeptide Y (NPY) receptor subtypes in porcine and canine peripheral tissues was performed. RT-PCR with Y 1 and Y 2 receptor-specific primers, indicated expression of Y 1 receptors in both kidney and spleen of dog and pig, and expression of Y 2 receptors in pig spleen. In pig kidney, expression of Y 1 receptor mRNA was located to intrarenal arteries, as demonstrated with in situ hybridization using human probes. The cloned and sequenced canine Y 1 , porcine Y 1 and Y 2 receptors revealed high homologies to previously characterized mammalian NPY receptors. Membrane and autoradiographic receptor-binding studies showed specific high-affinity binding sites for the purported Y 1 -selective radioligands 125 I-[Leu 31 Pro 34 ]peptide YY (PYY) and 3 H-BIBP 3226 in dog spleen, and for the putative Y 2 -selective 125 I-PYY(3–36) in dog and pig spleen. In the pig in vivo, [Leu 31 Pro 34 ]PYY, administered i.v., evoked vasoconstriction in spleen and kidney, actions that were potently inhibited by the non-peptide Y 1 receptor antagonist SR 120107A. In contrast, PYY(3–36) evoked vasoconstriction only in spleen and this effect was not influenced by SR 120107A. NPY evoked renal and splenic vasoconstriction in the dog in vivo, vascular responses that were inhibited by both BIBP 3226 and SR 120107A. Furthermore, the Y 1 receptor agonist [Leu 31 Pro 34 ]NPY also caused vasoconstriction in dog kidney and spleen, whereas the putative Y 2 agonist N -acetyl[Leu 28 Leu 31 ]NPY(24–36) evoked no such vascular responses. It is concluded that the pig spleen is likely to contain Y 1 and Y 2 receptors, both involved in splenic vasoconstriction. In contrast, the Y 1 receptor seems to be the sole vascular NPY receptor subtype in pig kidney. Moreover, Y 1 receptors predominate in dog spleen and kidney. Furthermore, the cloned canine Y 1 receptor and the porcine Y 1 and Y 2 receptors show great homologies to, and possess ligand requirement profiles in accordance with, the human forms. |
| Databáze: | OpenAIRE |
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