Evolution of neuropeptide Y, peptide YY and pancreatic polypeptide

Larhammar, Dan

doi:10.1016/0167-0115(95)00169-7

Cited by 361 publications

(230 citation statements)

References 69 publications

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“…NPY is one of the most evolutionarily highly conserved peptides known [43] and exerts its wide range of action in man via at least three different receptor subtypes, designated Y 1 -, Y 2 -, and Y 5 -receptors. One of the most striking neurotransmitter effects of NPY within the central nervous system is its involvement in the regulation of food intake and body weight.…”

Section: Discussionmentioning

confidence: 99%

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Söll

Dinger

Lundell

et al. 2001

European Journal of Biochemistry

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In contrast, cyclo S±S [Cys20,Cys24]pNPY was found to be a highly selective ligand at the Y 2 -receptor, binding only threefold less efficiently than NPY. Analogues containing variations of positions 31 and 32 showed highly reduced affinity to the Y 1 -receptor, while binding to the Y 5 -receptor was affected less. Inhibition of cAMP-accumulation of selected peptides with replacements within position 20±23 of NPY showed preserved agonistic properties. The NPY analogues tested give insights into ligand±receptor interaction of NPY at the Y 1 -, Y 2 -and Y 5 -receptor and contribute to our understanding of subtype selectivity. Furthermore, the Y 1 -receptor-preferring peptides are novel tools that will provide insight into the physiological role of the Y 1 -receptor.Keywords: food intake; neuropeptides; NPY; selective ligands; structure±affinity relationship.Obesity, food intake and energy homeostasis are key areas of growing importance because obesity is beginning to replace malnutrition and infectious diseases as the most significant contributor to ill health in the developed world [1]. Neuropeptide Y (NPY) is one of the most important effector molecules of leptin: it is a key molecule in the regulation of food intake, it acts via several different receptor subtypes and elicits several physiological effects. Profound effects on stimulation of food intake, secretion of luteinizing and growth hormone, and insulin release suggest an important role for NPY in the pathophysiology of obesity and diabetes [2±5]. A wide range of other effects of NPY have been reported, such as potent vasoconstriction [6], facilitation of learning and memory [7], modulation of locomotor behaviours [8], induction of hypothermia [9,10], inhibition of sexual behaviour [11], shifts in circadian rhythms [12], modulation of cardiorespiratory parameters[13], anxiolytic potency [14] and inhibition of alcohol consumption and resistance [15].NPY is a 36-amino acid peptide amide belonging to the family of pancreatic polypeptides that includes also pancreatic polypeptide (PP) and peptide YY; it was first isolated from pig brain in 1982 [16].NPY is widely distributed within the central nervous system and in the periphery. [25,26]. A putative Y 3 -receptor has been described only pharmacologically and no specific agonists or antagonists are known [27]. All receptors belong to the G-protein coupled receptor superfamily [28]. The correlation of a certain receptor subtype to a distinct physiological effect is not yet fully understood. Recent studies even suggest that different receptor subtypes redundantly mediate identical actions in a given system, as has been shown for the Y 1 -and Y 5 -receptor in the regulation of food intake [3]. Findings that deficiencies in either the Y 1 -or the Y 5 -receptors do not significantly impair the normal feeding response to fasting or NPY stimulation, strongly indicate that both Y receptors are involved in appetite regulation by NPY [29,30]. Selective receptor agonists or antagonists are useful tools with which to stu...

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Section: Discussionmentioning

confidence: 99%

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Söll

Dinger

Lundell

et al. 2001

European Journal of Biochemistry

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“…Neuropeptide Y (NPY), which is a member of the pancreatic polypeptide hormone family that also includes pancreatic polypeptide (PP) and peptide YY (PYY), is one of the most evolutionarily highly conserved peptides known (Larhammar, 1996). The peptide is widely distributed within the central and peripheral nervous systems in mammals.…”

Section: Introductionmentioning

confidence: 99%

Receptor subtypes Y₁ and Y₅ mediate neuropeptide Y induced feeding in the guinea‐pig

Lecklin

Lundell

Paananen

et al. 2002

British J Pharmacology

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1 Neuropeptide Y (NPY) is one of the most potent stimulants of food intake. It has been debated which receptor subtype mediates this response. Initially Y 1 was proposed, but later Y 5 was announced as a`feeding' receptor in rats and mice. Very little is known regarding other mammals. The present study attempts to characterize the role of NPY in feeding behaviour in the distantly related guinea-pig. When infused intracerebroventricularly, NPY dose-dependently increased food intake. 2 PYY, (Leu 31 ,Pro 34 )NPY and NPY(2 ± 36) stimulated feeding, whereas NPY(13 ± 36) had no e ect. These data suggest that either Y 1 or Y 5 receptors or both may mediate NPY induced food intake in guinea-pigs. 3 The Y 1 receptor antagonists, BIBO 3304 and H 409/22 displayed nanomolar a nity for the Y 1 receptor (K i values 1.1+0.2 nM and 5.6+0.9 nM, respectively), but low a nity for the Y 2 or Y 5 receptors. When guinea-pigs were pretreated with BIBO 3304 and H 409/22, the response to NPY was inhibited. 4 The Y 5 antagonist, CGP 71683A had high a nity for the Y 5 receptor (K i 1.3+0.05 nM) without having any signi®cant activities at the Y 1 and Y 2 receptors. When CGP 71683A was infused into brain ventricles, the feeding response to NPY was attenuated. 5 The present study shows that NPY stimulates feeding in guinea-pigs through Y 1 and Y 5 receptors. As the guinea-pig is very distantly related to the rat and mouse, this suggests that both Y 1 and Y 5 receptors may mediate NPY-induced hyperphagia also in other orders of mammals.

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“…The primary peptides under investigation have been insulin, glucagon (GLU), and glucagon-like peptide (GLP), somatostatin (SST), and members of pancreatic polypeptide (PP) family, namely neuropeptide tyrosine (NPY), pancreatic polypeptide (PP), and peptide tyrosine tyrosine (PYY). The underlying objectives of studies concerned with isolation and description of the primary structure are to explain both the biological activity of these hormones within the organisms in question and to compare amino acid sequences so as to expand our knowledge of molecular evolution of regulatory peptides (Conlon, 1995;Larhammar, 1996;Plisetskaya and Mommsen, 1996). Immunohistochemistry has been the primary tool for identifying the distribution of the endocrine cells within the stomach, intestine, and the endocrine pancreas, while electron microscopy and immunocytochemistry have been useful in defining the characteristics of the cell types.…”

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The endocrine cells in the gastroenteropancreatic system of the bowfin, Amia calva L.: An immunohistochemical, ultrastructural, and immunocytochemical analysis

Youson¹,

Al‐Mahrouki²,

Naumovski³

et al. 2001

Journal of Morphology

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The gastroenteropancreatic (GEP) endocrine system of bowfin (Amia calva) was described using light and electron microscopy and immunological methods. The islet organ (endocrine pancreas) consists of diffusely scattered, mostly small islets and isolated patches of cells among and within the exocrine acini. The islets are composed of abundant, centrally located B cells immunoreactive to bovine and lamprey insulin antisera and D cells showing a widespread distribution and specificity to somatostatin antibodies. A and F cells are present at the very periphery of the islets and are immunoreactive with antisera against glucagon (and glucagon-like peptide) and several peptides of the pancreatic polypeptide (PP)-family, respectively. The peptides of the two families usually collocates within the same peripheral islet cells and are the most common immunoreactive peptides present in the extra-islet tissue. Immunocytochemistry and fine structural observations characterised the granule morphology for B and D cells and identified two cell types with granules immunoreactive to glucagon antisera. These two putative A cells had similar granules, which were distinct from either B or D cells, but one of the cells had rodshaped cytoplasmic inclusions within cisternae of what appeared to be rough endoplasmic reticulum. The inclusions were not immunoreactive to either insulin or glucagon antisera. Only small numbers of cells in the stomach and intestine immunoreacted to antisera against somatostatin, glucagon, and PP-family peptides. The paucity of these cells was reflected in the low concentrations of these peptides in intestinal extracts. The GEP system of bowfin is not unlike that of other actinopterygian fishes, but there are some marked differences that may reflect the antiquity of this system and/or may be a consequence of the ontogeny of this system in this species.

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Evolution of neuropeptide Y, peptide YY and pancreatic polypeptide

Cited by 361 publications

References 69 publications

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Receptor subtypes Y₁ and Y₅ mediate neuropeptide Y induced feeding in the guinea‐pig

The endocrine cells in the gastroenteropancreatic system of the bowfin, Amia calva L.: An immunohistochemical, ultrastructural, and immunocytochemical analysis

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Evolution of neuropeptide Y, peptide YY and pancreatic polypeptide

Cited by 361 publications

References 69 publications

Novel analogues of neuropeptide Y with a preference for the Y1‐receptor

Novel analogues of neuropeptide Y with a preference for the Y1‐receptor

Receptor subtypes Y1 and Y5 mediate neuropeptide Y induced feeding in the guinea‐pig

The endocrine cells in the gastroenteropancreatic system of the bowfin, Amia calva L.: An immunohistochemical, ultrastructural, and immunocytochemical analysis

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Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Novel analogues of neuropeptide Y with a preference for the Y₁‐receptor

Receptor subtypes Y₁ and Y₅ mediate neuropeptide Y induced feeding in the guinea‐pig