» Articles » PMID: 23221599

PACAP Controls Adrenomedullary Catecholamine Secretion and Expression of Catecholamine Biosynthetic Enzymes at High Splanchnic Nerve Firing Rates Characteristic of Stress Transduction in Male Mice

Overview
Journal Endocrinology
Specialty Endocrinology
Date 2012 Dec 11
PMID 23221599
Citations 43
Authors
Affiliations
Soon will be listed here.
Abstract

The neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is a cotransmitter of acetylcholine at the adrenomedullary synapse, where autonomic regulation of hormone secretion occurs. We have previously reported that survival of prolonged metabolic stress in mice requires PACAP-dependent biosynthesis and secretion of adrenomedullary catecholamines (CAs). In the present experiments, we show that CA secretion evoked by direct high-frequency stimulation of the splanchnic nerve is abolished in native adrenal slices from male PACAP-deficient mice. Further, we demonstrate that PACAP is both necessary and sufficient for CA secretion ex vivo during stimulation protocols designed to mimic stress. In vivo, up-regulation of transcripts encoding adrenomedullary CA-synthesizing enzymes (tyrosine hydroxylase, phenylethanolamine N-methyltransferase) in response to both psychogenic and metabolic stressors (restraint and hypoglycemia) is PACAP-dependent. Stressor-induced alteration of the adrenomedullary secretory cocktail also appears to require PACAP, because up-regulation of galanin mRNA is abrogated in male PACAP-deficient mice. We further show that hypoglycemia-induced corticosterone secretion is not PACAP-dependent, ruling out the possibility that glucocorticoids are the main mediators of the aforementioned effects. Instead, experiments with bovine chromaffin cells suggest that PACAP acts directly at the level of the adrenal medulla. By integrating prolonged CA secretion, expression of biosynthetic enzymes and production of modulatory neuropeptides such as galanin, PACAP is crucial for adrenomedullary function. Importantly, our results show that PACAP is the dominant adrenomedullary neurotransmitter during conditions of enhanced secretory demand.

Citing Articles

Pituitary adenylyl cyclase-activating polypeptide modulates the stress response: the involvement of different brain areas and microglia.

Singh A, Shim P, Naeem S, Rahman S, Lutfy K Front Psychiatry. 2025; 15:1495598.

PMID: 39931196 PMC: 11807976. DOI: 10.3389/fpsyt.2024.1495598.


Adaptive remodeling of rat adrenomedullary stimulus-secretion coupling in a chronic hypertensive environment.

Paille V, Park J, Toutain B, Bourreau J, Fontanaud P, De Nardi F Cell Mol Life Sci. 2024; 82(1):31.

PMID: 39725761 PMC: 11671677. DOI: 10.1007/s00018-024-05524-5.


Cellular mechanisms underlying pituitary adenylate cyclase activating polypeptide-stimulated secretion in the adrenal medulla.

Bell N, Chen X, Giovannucci D, Anantharam A Biochem Soc Trans. 2024; 52(6):2373-2383.

PMID: 39656194 PMC: 11668280. DOI: 10.1042/BST20231326.


A PACAP-activated network for secretion requires coordination of Ca influx and Ca mobilization.

Chen X, Bell N, Coffman B, Rabino A, Garcia-Mata R, Kammermeier P Mol Biol Cell. 2024; 35(7):ar92.

PMID: 38758660 PMC: 11244167. DOI: 10.1091/mbc.E24-02-0083.


Serotonin and the serotonin transporter in the adrenal gland.

Bauer M, Currie K Vitam Horm. 2024; 124:39-78.

PMID: 38408804 PMC: 11217909. DOI: 10.1016/bs.vh.2023.06.002.


References
1.
Lehmann M, Mustafa T, Eiden A, Herkenham M, Eiden L . PACAP-deficient mice show attenuated corticosterone secretion and fail to develop depressive behavior during chronic social defeat stress. Psychoneuroendocrinology. 2012; 38(5):702-15. PMC: 3652373. DOI: 10.1016/j.psyneuen.2012.09.006. View

2.
Fischer-Colbrie R, Eskay R, Eiden L, MAAS D . Transsynaptic regulation of galanin, neurotensin, and substance P in the adrenal medulla: combinatorial control by second-messenger signaling pathways. J Neurochem. 1992; 59(2):780-3. DOI: 10.1111/j.1471-4159.1992.tb09440.x. View

3.
Hamelink C, Tjurmina O, Damadzic R, Young W, Weihe E, Lee H . Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis. Proc Natl Acad Sci U S A. 2002; 99(1):461-6. PMC: 117582. DOI: 10.1073/pnas.012608999. View

4.
Ceresini G, Sgoifo A, Freddi M, Musso E, Parmigiani S, Del Rio G . Effects of galanin and the galanin receptor antagonist galantide on plasma catecholamine levels during a psychosocial stress stimulus in rats. Neuroendocrinology. 1998; 67(1):67-72. DOI: 10.1159/000054300. View

5.
Holgert H, Holmberg K, Hannibal J, Fahrenkrug J, Brimijoin S, Hartman B . PACAP in the adrenal gland--relationship with choline acetyltransferase, enkephalin and chromaffin cells and effects of immunological sympathectomy. Neuroreport. 1996; 8(1):297-301. DOI: 10.1097/00001756-199612200-00059. View