Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms

Grundemar, Lars; Håkanson, R.

doi:10.1016/0306-3623(93)90151-m

Cited by 92 publications

(37 citation statements)

References 93 publications

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“…NPY is implicated in cardiovascular homeostasis because of its vasoconstrictive actions on blood vessels (4,6). Cardiac hypertrophy is thought to represent an adaptive process in response to increased workload.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors

Pellieux

Sauthier

Domenighetti

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors

Pellieux

Sauthier

Domenighetti

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…PYY-like immunoreactivity is found in endocrine cells of the lower gastrointestinal tract, and the peptide has been shown to have a variety of effects on gastrointestinal function (4, 5). NPY, which is the most highly conserved of the family members between species (6), is extensively distributed throughout both the central and the peripheral nervous systems (7,8). NPY is colocalized with norepinephrine in postganglionic sympathetic nerves (4) and is a potent vasopressor agent (9).…”

Section: Introductionmentioning

confidence: 99%

Cloning and functional expression of cDNAs encoding human and rat pancreatic polypeptide receptors.

Yan

Yang

Marasco

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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PCR was used to isolate nucleotide sequences that may encode novel members of the neuropeptide Y receptor family. By use of a PCR product as a hybridization probe, a full-length human cDNA was isolated that encodes a 375-aa protein with a predicted membrane topology identifying it as a member of the G-protein-coupled receptor superfamily. After stable transfection of the cDNA into human embryonic kidney 293 cells, the receptor exhibited high affinity (Kd = 2.8 nM) for 1251-labeled human pancreatic polypeptide (PP).Competition binding studies in whole cells indicated the following rank order of potency: human PP = bovine PP 2 human [Pro34] peptide YY > rat PP > human peptide VY = human neuropeptide Y. Northern blot analysis revealed that human PP receptor mRNA is most abundantly expressed in skeletal muscle and, to a lesser extent, in lung and brain tissue. A rat cDNA clone encoding a high-affinity PP receptor that is 74% identical to the human PP receptor at the amino acid level was also isolated. These receptor clones will be useful in elucidating the functional role of PP and designing selective PP receptor agonists and antagonists.Pancreatic polypeptide (PP), peptide YY (PYY), and neuropeptide Y (NPY) are C-terminal amidated, 36-aa peptides that constitute the mammalian NPY family (1). PP is produced predominantly by pancreatic islet cells and regulates pancreatic exocrine secretion through a mechanism that is not fully understood but may involve inhibition of vagal input to the pancreas (2, 3). PYY-like immunoreactivity is found in endocrine cells of the lower gastrointestinal tract, and the peptide has been shown to have a variety of effects on gastrointestinal function (4, 5). NPY, which is the most highly conserved of the family members between species (6), is extensively distributed throughout both the central and the peripheral nervous systems (7,8). NPY is colocalized with norepinephrine in postganglionic sympathetic nerves (4) and is a potent vasopressor agent (9). The observations of persistent vasoconstriction after a-adrenergic receptor blockade (10, 11) and elevated levels of NPY in hypertensive patients (10, 12) suggest a possible role for NPY in the pathophysiology of hypertension. In the central nervous system, NPY immunoreactivity and mRNA are prevalent in various hypothalamic nuclei, the cerebral cortex, and the septal-hippocampal system and striatum (5). Important effects of centrally administered NPY include hyperphagia (13), anxiolysis (14), and regulation of pituitary hormone release (15).Receptors for NPY/PYY have been delineated on the basis of pharmacological selectivity exhibited by certain tissues and cell lines. The Y1 receptor exhibits high affinity for NPY, PYY, and C-terminal-substituted variants, including [Leu3t,Pro34]NPY, but low affinity for long C-terminal fragments such as 17). This receptor, which is a member of the G-protein-coupled receptor superfamily, has been cloned (18), and its pharmacological properties in transfected cells are identical to those of Y1 rece...

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“…The Y1-R was first cloned (12)(13)(14). Pharmacological and physiological studies have shown that the constricting effect of NPY on blood vessels mainly is mediated by Y1-Rs (15,16), and this is also true for cerebral vessels (17,18). The cellular localization of Y1-R binding sites has been observed on vascular smooth muscle cells (SMCs) with autoradiographic ligand binding methodology (19)(20)(21), and Y1-R mRNA has been demonstrated in vascular SMCs (13,14) and with in situ hybridization in arterioles and small arteries in testis, ovary, and oviduct (22).…”

mentioning

confidence: 99%

Localization of neuropeptide Y Y1 receptors in cerebral blood vessels

Liu

Kopp

Zhang

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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The localization of neuropeptide Y (NPY) Y1 receptor (R) -like immunoreactivity (LI) has been studied in cerebral arteries and arterioles of the rat by immunohistochemistry using f luorescence, confocal, and electron microscopy. High levels of Y1-R-LI were observed in smooth muscle cells (SMCs) in the small arterioles of the pial arterial network, especially on the basal surface of the brain, and low levels in the major basal cerebral arteries. The levels of Y1-R-LI varied strongly between adjacent SMCs. Y1-R-LI was associated with small endocytosis vesicles, mainly on the outer surface of the SMCs, but also on their endothelial side and often laterally at the interface between two SMCs. NPYimmunoreactive (Ir) nerve fibers could not be detected in association with the Y1-R-rich small arterioles but only around arteries with low Y1-R levels. A dense network of central NPY-Ir nerve fibers in the superficial layers of the brain was lying close to the strongly Y1-R-Ir small arterioles. The results indicate that NPY has a profound effect on small arterioles of the brain acting on Y1-Rs, both on the peripheral and luminal side of the SMCs. However, the source of the endogenous ligand, NPY, remains unclear. NPY released from central neurons may play a role, in addition to blood-borne NPY.The extensive innervation of brain vessels by sympathetic noradrenergic nerves was described by Nielsen and Owman (1; also see ref.2). Neuropeptide Y (NPY) (3) coexists with noradrenaline (NA) in sympathetic neurons in general (4) and also in NA nerves around brain vessels (5, 6). NPY causes vasoconstriction (7), and potentiates NA-induced vasoconstriction (8), effects that also can be seen on brain vessels (5). NPY causes a reduction in cerebral blood flow after injection into the internal carotid artery (6). In addition, NPY is present in parasympathetic cholinergic neurons and cerebrovascular nerves (9, 10).Two types of NPY receptors were identified on pharmacological grounds as post-and prejunctional NPY receptors, referred to as Y1 and Y2 receptors (Y1-and Y2-Rs), respectively (11). The Y1-R was first cloned (12-14). Pharmacological and physiological studies have shown that the constricting effect of NPY on blood vessels mainly is mediated by 16), and this is also true for cerebral vessels (17, 18). The cellular localization of Y1-R binding sites has been observed on vascular smooth muscle cells (SMCs) with autoradiographic ligand binding methodology (19-21), and Y1-R mRNA has been demonstrated in vascular SMCs (13,14) and with in situ hybridization in arterioles and small arteries in testis, ovary, and oviduct (22). Y1-Rs and Y1-R mRNA have also been found in cerebral arteries (17,18). Recently, the localization of the Y1-R protein has been shown in sensory ganglia, spinal cord, and the brain (23), and in arterial SMCs in the testis (22) with an antiserum raised against the Y1-R.In the present study we have used an affinity-purified antiserum directed against a C-terminal peptide fragment of the Y1-R to study rat cerebral...

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Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms

Cited by 92 publications

References 93 publications

Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors

Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors

Cloning and functional expression of cDNAs encoding human and rat pancreatic polypeptide receptors.

Localization of neuropeptide Y Y1 receptors in cerebral blood vessels

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