Neuropeptide Y receptor subtypes, Y1 and Y2

Claes R Wahlestedt, L. Grundemar, R. Hakanson, M. Heilig, G. H. Shen, Z. Zukowska-Grojec, D. J. Reis

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

Heterogeneity among NPY (and PYY) receptors was first proposed on the basis of studies on sympathetic neuroeffector junctions, where NPY (and PYY) can exert three types of action: 1) a direct (e.g., vasoconstrictor) response; 2) a postjunctional potentiating effect on NE-evoked vasoconstriction; and 3) a prejunctional suppression of stimulated NE release; the two latter phenomena are probably reciprocal, since NE affect NPY mechanisms similarly. It was found that amidated C-terminal NPY (or PYY fragments, e.g., NPY 13-36, could stimulate selectively prejunctional NPY/PYY receptors, which were termed Y2-receptors. Consequently, the postjunctional receptors which were activated poorly by NPY/PYY fragments, were termed Y1-receptors. Later work has indicated that the Y2-receptor may occur postjunctionally in selected sympathetic effector systems. The central nervous system appears to contain a mixture of Y1- and Y2-receptors as indicated by functional as well as binding studies. For instance, NPY and NPY 13-36 produced diametrically opposite effects on behavioral activity, indicating the action of the parent peptide on two distinct receptors. Cell lines, most importantly neuroblastomas, with exclusive populations of Y1- or Y2-receptors, have been characterized by binding and second messenger studies. In this work, selective agonists for the two receptor subtypes were used. Work of many investigators has formed the basis for subclassifying NPY/PYY effects being mediated by either Y1- or Y2-receptors. A preliminary subclassification based on effects of NPY, PYY, fragments and/or analogs is provided in Table 6. It is, however, to be expected that further receptor heterogeneity will be revealed in the future. It is argued that mast cells possess atypical NPY/PYY receptors. The histamine release associated with stimulation of the latter receptors may, at least in part, underlie the capacity of NPY as well as of short C-terminal fragments to reduce blood pressure. Fragments, such as NPY 22-36, appear to be relatively selective vasodepressor agents because of their weak vasopressor properties. Finally, as a result of attempts to expression clone NPY/PYY receptor(s), we have, by use of Xenopus oocytes, designed a few strategies to detect de novo NPY/PYY receptor expression. Thus, it is suggested that mRNA derived from lung and neuroblastoma cell lines may confer NPY responsiveness to the oocytes as assessed by electrophysiological and second messenger studies.

Original languageEnglish
Pages (from-to)7-26
Number of pages20
JournalAnnals of the New York Academy of Sciences
Volume611
StatePublished - Dec 1 1990
Externally publishedYes

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Neuropeptide Y Receptors
Second Messenger Systems
Neuroblastoma
Oocytes
Neuroeffector Junction
Cells
Cell Line
Histamine Release
Blood pressure
Neurology
Vasoconstrictor Agents
Xenopus
Vasoconstriction
Mast Cells
Histamine
Central Nervous System
Clone Cells
Research Personnel
peptide YY receptor
neuropeptide Y-Y1 receptor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wahlestedt, C. R., Grundemar, L., Hakanson, R., Heilig, M., Shen, G. H., Zukowska-Grojec, Z., & Reis, D. J. (1990). Neuropeptide Y receptor subtypes, Y1 and Y2. Annals of the New York Academy of Sciences, 611, 7-26.

Neuropeptide Y receptor subtypes, Y1 and Y2. / Wahlestedt, Claes R; Grundemar, L.; Hakanson, R.; Heilig, M.; Shen, G. H.; Zukowska-Grojec, Z.; Reis, D. J.

In: Annals of the New York Academy of Sciences, Vol. 611, 01.12.1990, p. 7-26.

Research output: Contribution to journalArticle

Wahlestedt, CR, Grundemar, L, Hakanson, R, Heilig, M, Shen, GH, Zukowska-Grojec, Z & Reis, DJ 1990, 'Neuropeptide Y receptor subtypes, Y1 and Y2', Annals of the New York Academy of Sciences, vol. 611, pp. 7-26.
Wahlestedt CR, Grundemar L, Hakanson R, Heilig M, Shen GH, Zukowska-Grojec Z et al. Neuropeptide Y receptor subtypes, Y1 and Y2. Annals of the New York Academy of Sciences. 1990 Dec 1;611:7-26.
Wahlestedt, Claes R ; Grundemar, L. ; Hakanson, R. ; Heilig, M. ; Shen, G. H. ; Zukowska-Grojec, Z. ; Reis, D. J. / Neuropeptide Y receptor subtypes, Y1 and Y2. In: Annals of the New York Academy of Sciences. 1990 ; Vol. 611. pp. 7-26.
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