ArticleProceedings of the National Academy of Sciences of the United States of America2002
Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 250 citations in OpenAlex.
- Pooled it
- Catecholamine metabolism revisited: from neurochemistry to integrative physiology and pathophysiology.Physiological reviews · 2026Review
- Article
- A chemogenetic approach for temporal and cell-specific activation of endogenous GPCRs in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Roles for PKC signaling in chromaffin cell exocytosis.Biophysical journal · 2025Article
- Cellular mechanisms underlying pituitary adenylate cyclase activating polypeptide-stimulated secretion in the adrenal medulla.Biochemical Society transactions · 2024Review
- TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia.The EMBO journal · 2024Article
- A PACAP-activated network for secretion requires coordination of CaMolecular biology of the cell · 2024Article
- Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure-A Diabetic Perspective.Metabolites · 2024Review
- Pituitary adenylyl cyclase-activating polypeptide modulates the stress response: the involvement of different brain areas and microglia.Frontiers in psychiatry · 2024Review
- PAC1 deficiency reduces chondrogenesis in atherosclerotic lesions of hypercholesterolemic ApoE-deficient mice.BMC cardiovascular disorders · 2023Article
- Constitutive and conditional deletion reveals distinct phenotypes driven by developmental versus neurotransmitter actions of the neuropeptide PACAP.Journal of neuroendocrinology · 2023Article
- Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Sudden Infant Death Syndrome: A Potential Model for Investigation.International journal of molecular sciences · 2023Review
- PACAP Controls Endocrine and Behavioral Stress Responses via Separate Brain Circuits.Biological psychiatry global open science · 2023Article
- The functional heterogeneity of PACAP: Stress, learning, and pathology.Neurobiology of learning and memory · 2023Review
- PACAP and VIP Neuropeptides' and Receptors' Effects on Appetite, Satiety and Metabolism.Biology · 2023Review
- The metabolic cost of physical activity in mice using a physiology-based model of energy expenditure.Molecular metabolism · 2023Article
- PACAP and acetylcholine cause distinct Ca2+ signals and secretory responses in chromaffin cells.The Journal of general physiology · 2023Article
- PACAP regulates VPAC1 expression, inflammatory processes and lipid homeostasis in M1- and M2-macrophages.Frontiers in cardiovascular medicine · 2023Article
- Neuropeptides and small-molecule amine transmitters: cooperative signaling in the nervous system.Cellular and molecular life sciences : CMLS · 2022Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The adrenal gland is important for homeostatic responses to metabolic stress: hypoglycemia stimulates the splanchnic nerve, epinephrine is released from adrenomedullary chromaffin cells, and compensatory glucogenesis ensues. Acetylcholine is the primary neurotransmitter mediating catecholamine secretion from the adrenal medulla. Accumulating evidence suggests that a secretin-related neuropeptide also may function as a transmitter at the adrenomedullary synapse. Costaining with highly specific antibodies against the secretin-related neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) and the vesicular acetylcholine transporter (VAChT) revealed that PACAP is found in nerve terminals at all mouse adrenomedullary cholinergic synapses. Mice with a targeted deletion of the PACAP gene had otherwise normal cholinergic innervation and morphology of the adrenal medulla, normal adrenal catecholamine and blood glucose levels, and an intact initial catecholamine secretory response to insulin-induced hypoglycemia. However, insulin-induced hypoglycemia was more profound and longer-lasting in PACAP knock-outs, and was associated with a dose-related lethality absent in wild-type mice. Failure of PACAP-deficient mice to adequately counterregulate plasma glucose levels could be accounted for by impaired long-term secretion of epinephrine, secondary to a lack of induction of tyrosine hydroxylase, normally occurring after insulin hypoglycemia in wild-type mice, and a consequent depletion of adrenomedullary epinephrine stores. Thus, PACAP is needed to couple epinephrine biosynthesis to secretion during metabolic stress. PACAP appears to function as an "emergency response" cotransmitter in the sympathoadrenal axis, where the primary secretory response is controlled by a classical neurotransmitter but sustained under paraphysiological conditions by a neuropeptide.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.