Pituitary adenylate cyclase‐activating peptide: Potential roles in the pathophysiology and complications of cirrhosis

Barloese, Mads; Chitgar, Mohammadnavid; Hannibal, Jens; Möller, Sören

doi:10.1111/liv.14602

Cited by 4 publications

(2 citation statements)

References 149 publications

(279 reference statements)

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“…It also triggers the activation of phospholipase C, which leads to the breakdown of phosphatidyl inositol 4,5-bisphosphate (PIP2) into inositol triphosphate and diacylglycerol (DAG), which activates protein kinase C (PKC) [100]. On the other hand, VPAC1 and VPAC2 receptor activation leads to AC enzyme activation, which leads to the generation of cAMP and the activation of PKA [101]. Also, PACAP signaling turns on calcium signaling, which causes intracellular calcium to be released and calcium/calmodulin-dependent kinase II to be activated [102].…”

Section: Receptor and Signaling Mechanisms Of Pacap And Vipmentioning

confidence: 99%

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment

Tanaka,

Szabó,

Körtési

et al. 2023

Cells

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Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nonetheless, newly approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have a 50% responder rate ranging from 27 to 71.0%, whereas CGRP receptor inhibitors have a 50% responder rate ranging from 56 to 71%. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge of PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.

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Section: Receptor and Signaling Mechanisms Of Pacap And Vipmentioning

confidence: 99%

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment

Tanaka,

Szabó,

Körtési

et al. 2023

Cells

View full text Add to dashboard Cite

show abstract

“…It also triggers the activation of phospholipase C, which leads to the breakdown of phosphatidyl inositol 4,5-bisphosphate (PIP2) into inositol triphosphate and diacylglycerol (DAG), which activates protein kinase C (PKC) [94]. On the other hand, VPAC1 and VPAC2 receptor activation leads to AC enzyme activation, which leads to the generation of cAMP and the activation of PKA [95]. Also, PACAP signaling turns on calcium signaling, which causes intracellular calcium to be released and calcium/calmodulin-dependent kinase II to be activated [96].…”

Section: Receptor and Signaling Mechanisms Of Pacapmentioning

confidence: 99%

From CGRP to PACAP: Unraveling the Next Chapter in Migraine Treatment

Tanaka,

Szabó,

Körtési

et al. 2023

Preprint

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Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. However, the efficacy of calcitonin gene-related peptide (CGRP) receptor antagonists and monoclonal antibodies (mAbs) in treating migraines can vary among patients, and tolerance may develop over time, reducing their effectiveness. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Animal models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology. Intriguingly, the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. In addition, another secretin family peptide vasoactive intestinal peptide is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment. Recent findings highlight the importance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to anti-CGRP therapies. By updating our knowledge on PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides as a novel treatment approach for migraines.

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Decreased Plasma Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Levels are Linked with Disease Severity in Patients with Liver Cirrhosis

Yang

Hou

Han

et al. 2021

Int J Pept Res Ther

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Pituitary adenylate cyclase‐activating peptide: Potential roles in the pathophysiology and complications of cirrhosis

Cited by 4 publications

References 149 publications

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment

From CGRP to PACAP: Unraveling the Next Chapter in Migraine Treatment

Decreased Plasma Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Levels are Linked with Disease Severity in Patients with Liver Cirrhosis

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