The functional heterogeneity of PACAP: Stress, learning, and pathology

Rajbhandari, Abha K.; Barson, Jessica R.; Gilmartin, Marieke R.; Hammack, Sayamwong E.; Chen, Briana K.

doi:10.1016/j.nlm.2023.107792

Cited by 4 publications

(2 citation statements)

References 215 publications

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“…While the actions of acetylcholine in the medulla have been interrogated for many decades, beginning with the work of Feldberg in the 1930s (Feldberg et al, 1934), the studies of PACAP-stimulated secretion are still very much at a nascent stage. Indeed, our knowledge of PACAP and its physiological effects, particularly in the context of stress transduction, are much more advanced elsewhere in the body than it is in the adrenal (Rajbhandari et al, 2023; Riser and Norrholm, 2022). In the central nervous system (CNS), PACAP was originally identified as a peptide in the hypothalamus and shown to stimulate adenylate cyclase activity in the anterior pituitary gland (Miyata et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to acetylcholine – which causes membrane depolarization, the opening of voltage-gated channels, and dense core vesicle fusion – the mechanisms coupling PACAP stimulation in the chromaffin cell to fusion remain poorly understood (Carbone et al, 2019; Eiden et al, 2018). The specific intracellular consequences of PACAP stimulation appear to vary by cell-type and system, with Gα q and Gα s proteins being implicated in its signaling pathways (Rajbhandari et al, 2023). However, it has been clear from the earliest studies of PACAP action that the secretion it provokes is Ca 2+ -dependent (Chowdhury et al, 1994; Przywara et al, 1996; Watanabe et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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A PACAP-activated network for secretion requires coordination of Ca²⁺influx and Ca²⁺mobilization

Chen,

Bell,

Coffman

et al. 2024

Preprint

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Chromaffin cells of the adrenal medulla transduce sympathetic nerve activity into stress hormone secretion. The two neurotransmitters principally responsible for coupling cell stimulation to secretion are acetylcholine and pituitary adenylate activating polypeptide (PACAP). In contrast to acetylcholine, PACAP evokes a persistent secretory response from chromaffin cells. However, the mechanisms by which PACAP acts are poorly understood. Here, it is shown that PACAP induces sustained increases in cytosolic Ca2+which are disrupted when Ca2+influx through L-type channels is blocked or internal Ca2+stores are depleted. PACAP liberates stored Ca2+via inositol trisphosphate receptors (IP3Rs) on the endoplasmic reticulum (ER), thereby functionally coupling Ca2+mobilization to Ca2+influx and supporting Ca2+-induced Ca2+-release. These Ca2+influx and mobilization pathways are unified by an absolute dependence on phospholipase C epsilon (PLCε) activity. Thus, the persistent secretory response that is a defining feature of PACAP activity,in situ, is regulated by a signaling network that promotes sustained elevations in intracellular Ca2+through multiple pathways.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A PACAP-activated network for secretion requires coordination of Ca²⁺influx and Ca²⁺mobilization

Chen,

Bell,

Coffman

et al. 2024

Preprint

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Psychodermatology of Chronic Pruritus: An Overview of the Link Between Itch and Distress

Ferreira,

Katamanin,

Jafferany

et al. 2024

Dermatol Ther (Heidelb)

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Chronic pruritus (CP) is defined as an unpleasant sensation causing a desire to scratch and lasting > 6 weeks. It has a multifactorial etiology but is more frequently associated with chronic inflammatory dermatoses and systemic disorders. Psychogenic pruritus and neurological disorders are other less common etiologies, while, in some patients, it is idiopathic. CP appears to be processed by non-histaminergic pathway, contributing to its complexity and therapeutic challenge. Moreover, regardless of the etiology, it is multidimensional, including cognitive, motivational and affective components. There is a close link between psychological distress and pruritus, with particular clinical expression in chronic inflammatory dermatoses, involving the activation of the hypothalamic-pituitary-adrenal axis (and its cutaneous equivalent), the sympathetic nervous system, the release of hormones and peptides, the role of immune cells (T and B cells, macrophages) and immune-related cells in the skin (mast cells, dendritic cells and keratinocytes). Moreover, there is strong evidence that psychological factors influence the experience of pruritus. CP can also cause psychiatric disorders, including but not limited to anxiety and depression, and also lead to significant quality of life (QoL) impairment. Thereby, although a psychodermatological assessment should ideally be carried out in the context of a specific psychodermatology consultation, a brief mental health assessment could be part of the general dermatological approach to these patients. Considering that mental health, QoL and pruritus are closely linked, psychotherapeutic interventions and/or psychotropic drugs should thus be considered in some patients as an adjunct to the pharmacological treatment of CP.

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Injectable Gel-PEG hydrogels as promising delivery system for intravitreal PACAP release: Novel therapeutics for unilateral common carotid artery occlusion induced retinal ischemia

Chen,

Liang,

Chen

et al. 2024

Biomedicine & Pharmacotherapy

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The functional heterogeneity of PACAP: Stress, learning, and pathology

Cited by 4 publications

References 215 publications

A PACAP-activated network for secretion requires coordination of Ca²⁺influx and Ca²⁺mobilization

A PACAP-activated network for secretion requires coordination of Ca²⁺influx and Ca²⁺mobilization

Psychodermatology of Chronic Pruritus: An Overview of the Link Between Itch and Distress

Injectable Gel-PEG hydrogels as promising delivery system for intravitreal PACAP release: Novel therapeutics for unilateral common carotid artery occlusion induced retinal ischemia

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The functional heterogeneity of PACAP: Stress, learning, and pathology

Cited by 4 publications

References 215 publications

A PACAP-activated network for secretion requires coordination of Ca2+influx and Ca2+mobilization

A PACAP-activated network for secretion requires coordination of Ca2+influx and Ca2+mobilization

Psychodermatology of Chronic Pruritus: An Overview of the Link Between Itch and Distress

Injectable Gel-PEG hydrogels as promising delivery system for intravitreal PACAP release: Novel therapeutics for unilateral common carotid artery occlusion induced retinal ischemia

Contact Info

Product

Resources

About

A PACAP-activated network for secretion requires coordination of Ca²⁺influx and Ca²⁺mobilization

A PACAP-activated network for secretion requires coordination of Ca²⁺influx and Ca²⁺mobilization