ADCYAP1 - adenylate cyclase activating polypeptide 1 ( RECEPTOR) | Elisa - Clia - Antibody - Protein

Background

Adenylate Cyclase Activating Polypeptide 1 (ADCYAP1) is a neuropeptide that acts as a ligand for its receptor, ADCYAP1 receptor. It plays crucial roles in regulating various physiological processes, including neurotransmission, neuroprotection, and modulation of the stress response. The ADCYAP1 receptor, also known as PAC1 receptor, is widely distributed throughout the central nervous system and peripheral tissues, indicating its diverse functions. Upon binding of ADCYAP1 to its receptor, intracellular signaling pathways are activated, leading to the production of cyclic adenosine monophosphate (cAMP) and subsequent activation of protein kinase A (PKA) and other downstream effectors. This signaling cascade influences synaptic transmission, neuronal excitability, and cellular responses to stressors. Dysregulation of ADCYAP1 signaling has been implicated in various neurological and psychiatric disorders, including anxiety, depression, and neurodegenerative diseases. Understanding the mechanisms underlying ADCYAP1 receptor activation provides insights into its physiological functions and potential therapeutic targets for neurological and psychiatric disorders. Ongoing research aims to elucidate the roles of ADCYAP1 signaling in health and disease, paving the way for the development of novel treatment strategies.

Protein Structure

PACAP is derived from a larger precursor protein and is characterized by:

• Peptide Hormone Structure: PACAP-38 and PACAP-27 share a common N-terminal sequence, with PACAP-38 being the longer form.
• Highly Conserved Sequence: PACAP shows a high degree of conservation across species, indicating its critical biological functions.

Function and Biological Significance

PACAP (ADCYAP1) exerts its effects primarily through the activation of G-protein-coupled receptors (GPCRs), leading to adenylate cyclase activation and increased cAMP production:

1. Neurotransmission and Neuroprotection: PACAP is widely distributed in the brain and spinal cord, where it modulates neurotransmitter release, neuroplasticity, and provides neuroprotective effects against injury and neurodegenerative conditions.
2. Hormone Regulation: PACAP regulates the secretion of various hormones including growth hormone, prolactin, and adrenocorticotropic hormone (ACTH), influencing pituitary function.
3. Vasodilation and Blood Flow: PACAP induces vasodilation, contributing to the regulation of blood flow and vascular tone.
4. Immune System Modulation: PACAP has immunomodulatory effects, influencing cytokine production and immune cell activity.

Interactions

PACAP interacts with specific receptors and signaling pathways to mediate its effects:

1. PAC1 Receptor (PAC1-R): The primary receptor for PACAP, highly specific and has high affinity for both PACAP-38 and PACAP-27.
2. VPAC1 and VPAC2 Receptors: These receptors also bind PACAP and VIP (vasoactive intestinal peptide), mediating a range of physiological effects.
3. GPCR Signaling: Binding of PACAP to its receptors activates adenylate cyclase via G-proteins, increasing intracellular cAMP levels and activating protein kinase A (PKA).
4. Interaction with Neuropeptides: PACAP can modulate the activity of other neuropeptides and neurotransmitters, influencing broader neuroendocrine functions.

Clinical Significance

Dysregulation of PACAP signaling is associated with various clinical conditions:

1. Migraine: Elevated levels of PACAP have been linked to migraine attacks, making it a potential target for migraine therapies.
2. Neurodegenerative Diseases: PACAP’s neuroprotective effects suggest potential therapeutic roles in conditions like Alzheimer’s disease and Parkinson’s disease.
3. Psychiatric Disorders: Alterations in PACAP signaling have been implicated in stress-related disorders, depression, and anxiety.
4. Inflammatory and Immune Disorders: PACAP’s role in modulating immune responses suggests potential applications in treating inflammatory diseases and immune dysregulation.

Summary

ADCYAP1, or PACAP, is a multifunctional neuropeptide with widespread effects on neurotransmission, hormone regulation, vasodilation, and immune modulation. Through its interactions with specific GPCRs, PACAP activates adenylate cyclase, leading to increased cAMP production and activation of downstream signaling pathways. Understanding the roles of PACAP in physiological and pathological conditions offers insights into its potential as a therapeutic target for a range of diseases, including migraines, neurodegenerative diseases, psychiatric disorders, and inflammatory conditions.