Prolactin‐Releasing Peptide Regulates the Cardiovascular System Via Corticotrophin‐Releasing Hormone

Abstract

Prolactin-releasing peptide (PrRP)-producing neurones are known to be localised mainly in the medulla oblongata and to act as a stress mediator in the central nervous system. In addition, central administration of PrRP elevates the arterial pressure and heart rate. However, the neuronal pathway of the cardiovascular effects of PrRP has not been revealed. In the present study, we demonstrate that PrRP-immunoreactive neurones projected to the locus coeruleus (LC) and the paraventricular nucleus (PVN) of the hypothalamus. The c-fos positive neurones among the noradrenaline cells in the LC, and the parvo- and magnocellular neurones in the PVN, were increased after central administration of PrRP. The arterial pressure and heart rate were both elevated after i.c.v. administration of PrRP. Previous studies have demonstrated that PrRP stimulated the neurones in the PVN [i.e. oxytocin-, vasopressin- and corticotrophin-releasing hormone (CRH)-producing neurones], which suggests that PrRP may induce its cardiovascular effect via arginine vasopressin (AVP) or CRH. Although the elevation of blood pressure and heart rate elicited by PrRP administration were not inhibited by an AVP antagonist, they were completely suppressed by treatment with a CRH antagonist. Thus, we conclude that PrRP stimulated CRH neurones in the PVN and that CRH might regulate the cardiovascular system via the sympathetic nervous system.

Hindbrain noradrenergic A2 neurons: diverse roles in autonomic, endocrine, cognitive, and behavioral functions

“…As mentioned previously, A2 neurons coexpress PrRP immunolabeling (52), and the LC contains PrRP-positive fibers and terminals as well as the receptor (UHR-1) for PrRP (284). While the evidence is indirect, these findings indicate that A2 neurons may provide modulatory control over NA neurons within the LC, thereby indirectly modifying NA signaling within cortical, hippocampal, amygdalar, thalamic, and cerebellar targets of the LC.…”

“…In addition, virtually all A2 neurons are immunoreactive for prolactin-releasing peptide (PrRP) (52). PrRP receptors are expressed within the paraventricular nucleus of the hypothalamus (PVN) and other brain regions targeted by A2 neurons (284), and there is evidence that PrRP acts synergistically with NE to activate hypophysiotropic corticotropin-releasing hormone (CRH) neurons at the apex of the hypothalamic-pituitary-adrenal (HPA) axis (147,261). Interestingly, the ratios of PrRP to NA biosynthetic enzymes in A2 neurons are modulated by estrogen and stress (235), and A2 neurons express receptors for estrogen and glucocorticoids (56,101,198,243).…”

Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats

“…Recently, it has been established that PrRP has other physiological functions (Onaka et al 2010), including the regulation of food intake (Lawrence et al 2000) and energy expenditure (Takayanagi et al 2008), whereas its involvement in the regulation of hypothalamic-pituitary-adrenal (HPA) axis (Dodd & Luckman 2013) and its prolactin-releasing ability was questioned (Jarry et al 2000). PrRP-producing cells are localized in the dorsomedial hypothalamic nucleus and in A1/A2 regions of the medulla oblongata (Yamada et al 2009) in the brainstem. The fibers of these cells project to the paraventricular nucleus (PVN), the basal nucleus of the amygdala, and other regions throughout the brain (Yamada et al 2009), suggesting that PrRP acts mainly in the central nervous system (CNS).…”

“…PrRP-producing cells are localized in the dorsomedial hypothalamic nucleus and in A1/A2 regions of the medulla oblongata (Yamada et al 2009) in the brainstem. The fibers of these cells project to the paraventricular nucleus (PVN), the basal nucleus of the amygdala, and other regions throughout the brain (Yamada et al 2009), suggesting that PrRP acts mainly in the central nervous system (CNS). It has been shown in rodents that intracerebroventricular injection of PrRP decreased food intake and body weight .…”

Central Regulation of Stress Response in Cattle

“…The highly expressed PrRP receptor in the paraventricular nucleus of the hypothalamus 37 , increased c-fos expression in the PrRP neuron after foot shock and restraint stressors 29,57 and increased plasma adrenocorticotropic hormone and corticosterone con centrations in rats after the intracerebroventricular administration of PrRP 24 , indicates the possible role of this receptor in the regulation of the HPA axis. The PrRP receptor also regulates energy expenditure via central CRH receptors 22 and stimulates the sympathetic nervous system through CRH neurons to increase body temperature, heart rate, and blood pres sure 22,50 . To date, little data have been published regarding the role of central PrRP in ruminants.…”