NPY and Stress 30 Years Later: The Peripheral View

Abstract

Almost 30 years ago, neuropeptide Y (NPY) was discovered as a sympathetic co-transmitter and one of the most evolutionarily conserved peptides abundantly present all over the body. Soon afterward, NPY’s multiple receptors were characterized and cloned, and the peptide’s role in stress was first documented. NPY has proven to be pivotal for maintaining many stress responses. Most notably, NPY is known for activating long-lasting vasoconstriction in many vascular beds, including coronary arteries. More recently, NPY was found to play a role in stress-induced accretion of adipose tissue which many times can lead to detrimental metabolic changes. It is however due to its prominent actions in the brain, one of which is its powerful ability to stimulate appetite as well as its anxiolytic activities that NPY became a peptide of importance in neuroscience. In contrast, its actions in the rest of the body, including its role as a stress mediator, remained, surprisingly underappreciated and not well understood. Our research has focused on that other, “peripheral” side of NPY. In this review, we will discuss those actions of NPY on the cardiovascular system and metabolism, as they relate to adaptation to stress, and attempt to both distinguish NPY’s effects from and integrate them with the effects of the classical stress mediators, glucocorticoids, and catecholamines. To limit the bias of someone (ZZ) who has viewed the world of stress through the eyes of NPY for over 20 years, fresh insight (DH) has been solicited to more objectively assess NPY’s contributions to stress-related diseases and the body’s ability to adapt to stress.

Neuropeptide Y1 receptor inhibits cell growth through inactivating mitogen-activated protein kinase signal pathway in human hepatocellular carcinoma

“…Neuropeptide Y (NPY) is a 36 amino acid peptide which belongs to the pancreatic polypeptide (PPY) family and exhibits 70 % amino acid sequence homology with peptide YY (PYY) and 50 % to PPY [11]. It is the most abundant neuropeptide in the mammalian brain and plays an important role in the feeding behavior, depression and stress, and the release of hypothalamic and pituitary hormones [12]. NPY is costored and co-released with norepinephrine in the sympathetic nerve endings.…”

Acupuncture in the Treatment of Cancer-Related Psychological Symptoms

“…Neuropeptide Y is thought to be pivotal in the stress response, with functions that include increasing food intake and fat storage, reducing anxiety, stress, and the perception of pain, and affecting circadian rhythms. 35 One immunohistochemical study demonstrated an increase in neuropeptide Y immunoreactive cells in the hippocampus, associated with increase in locomotion and weight as compared with control in maternally separated rats treated with a single acupuncture point. 36 Additional potential mechanisms of action stem from evidence that acupuncture can increase adrenocorticotropic hormone, a substance integral to the stress response, β-endorphins-the neurotransmitters associated with pain relief and a sense of well-being-as well as the neurotransmitters serotonin, dopamine and norepinephrine, all important targets in the psychiatric treatment of depression and anxiety.…”

Neuropeptides and the Microbiota-Gut-Brain Axis

“…CRF is a neuropeptide and gut hormone that is intimately related to stress, and there is considerable evidence that activation of peripheral CRF receptors contributes to stress-related alterations of gut physiology [126]. NPY may likewise be involved because it appears to mediate the effects of stress on many physiological systems including the gastrointestinal and immune systems [128,129]. For instance, deletion of NPY alters gastrointestinal, feeding and corticosterone responses to restraint stress, exaggerates stressinduced defaecation and reduces food intake [128].…”