scholarly journals Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase

2011 ◽  
Vol 105 (5) ◽  
pp. 2289-2296 ◽  
Author(s):  
Sungwon An ◽  
Robert P. Irwin ◽  
Charles N. Allen ◽  
Connie Tsai ◽  
Erik D. Herzog
Keyword(s):  
Adenylate Cyclase ◽  
Phospholipase C ◽  
Vasoactive Intestinal Polypeptide ◽  
Transcriptional Repression ◽  
Single Cells ◽  
Cell Types ◽  
Intracellular Camp ◽  
Dependent Manner ◽  
Environmental Light ◽  
Intestinal Polypeptide

Circadian oscillations in the suprachiasmatic nucleus (SCN) depend on transcriptional repression by Period (PER)1 and PER2 proteins within single cells and on vasoactive intestinal polypeptide (VIP) signaling between cells. Because VIP is released by SCN neurons in a circadian pattern, and, after photic stimulation, it has been suggested to play a role in the synchronization to environmental light cycles. It is not known, however, if or how VIP entrains circadian gene expression or behavior. Here, we tested candidate signaling pathways required for VIP-mediated entrainment of SCN rhythms. We found that single applications of VIP reset PER2 rhythms in a time- and dose-dependent manner that differed from light. Unlike VIP-mediated signaling in other cell types, simultaneous antagonism of adenylate cyclase and phospholipase C activities was required to block the VIP-induced phase shifts of SCN rhythms. Consistent with this, VIP rapidly increased intracellular cAMP in most SCN neurons. Critically, daily VIP treatment entrained PER2 rhythms to a predicted phase angle within several days, depending on the concentration of VIP and the interval between VIP applications. We conclude that VIP entrains circadian timing among SCN neurons through rapid and parallel changes in adenylate cyclase and phospholipase C activities.

Effects of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide on cyclic AMP accumulation in sheep pituitary cells in vitro

1996 ◽  
Vol 148 (3) ◽  
pp. 545-552 ◽  
Author(s):  
K Sawangjaroen ◽  
C Sernia ◽  
J D Curlewis
Keyword(s):  
Adenylate Cyclase ◽  
Vasoactive Intestinal Polypeptide ◽  
Rapid Development ◽  
Intracellular Camp ◽  
Type I ◽  
Pituitary Cells ◽  
Camp Accumulation ◽  
Pituitary Adenylate Cyclase ◽  
Camp Levels ◽  
Intestinal Polypeptide

Abstract Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are known to stimulate adenylate cyclase activity in rat pituitary cells but no direct effects have been reported on sheep pituitary cells. In this study we determined whether either peptide could stimulate intracellular cAMP accumulation in dispersed sheep pituitary cells in primary culture. Time course studies with PACAP showed that tachyphylaxis developed rapidly and so a short incubation time (5 min) was used to define the dose–response relationship. PACAP dose-dependently stimulated intracellular cAMP levels with a half-maximum response at 2·9 ± 0·2 nmol/l (n=4). In contrast, VIP only caused a small increase in intracellular cAMP levels at the highest dose tested (1 μmol/l). The VIP antagonist [4C1-d-Phe6,Leu17]VIP had no effect on the cAMP response to either PACAP or VIP while the peptide PACAP(6–38), a putative PACAP antagonist, blocked the cAMP response to PACAP. The desensitisation to PACAP was further investigated by pretreating cells with PACAP for 30 min. After a further 15 min in culture medium alone, these cells showed no cAMP response to subsequent treatment with PACAP but could respond to forskolin. When a longer incubation period of 240 min was used between the first and second treatment with PACAP, a partial return in responsiveness to PACAP was observed. In summary, these results show that PACAP activates adenylate cyclase in sheep pituitary cells but that there is rapid development of tachyphylaxis. Experiments with the antagonists suggest that the response to PACAP is via the PACAP type I receptor. In contrast, physiological doses of VIP do not stimulate cAMP accumulation in sheep pituitary cells. Journal of Endocrinology (1996) 148, 545–552

scholarly journals Mechanisms of Phospholipase C Activation by the Vasoactive Intestinal Polypeptide/Pituitary Adenylate Cyclase-Activating Polypeptide Type 2 Receptor

Endocrinology ◽  
2001 ◽  
Vol 142 (3) ◽  
pp. 1209-1217 ◽  
Author(s):  
Christopher J. MacKenzie ◽  
Eve M. Lutz ◽  
Melanie S. Johnson ◽  
Derek N. Robertson ◽  
Pamela J. Holland ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Phospholipase C ◽  
Vasoactive Intestinal Polypeptide ◽  
Pituitary Adenylate Cyclase ◽  
Intestinal Polypeptide

VASOACTIVE INTESTINAL POLYPEPTIDE STIMULATES ADENYLATE CYCLASE AND SEROTONIN N-ACETYLTRANSFERASE ACTIVITIES IN RAT PINEAL IN VITRO

1980 ◽  
Vol 1 (1) ◽  
pp. 84-87 ◽  
Author(s):  
TOSHIO KANEKO ◽  
PO-YUAN CHENG ◽  
HIROSHI OKA ◽  
TOSHITSUGU ODA ◽  
NOBORU YANAIHARA ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Vasoactive Intestinal Polypeptide ◽  
Intestinal Polypeptide

Phospholipids stabilize binding of pituitary adenylate cyclase-activating peptide to vasoactive intestinal polypeptide receptor

2021 ◽  
Author(s):  
Nidhin Thomas ◽  
Ashutosh Agrawal
Keyword(s):  
Adenylate Cyclase ◽  
Receptor Binding ◽  
Vasoactive Intestinal Polypeptide ◽  
Binding Free Energy ◽  
Active Role ◽  
Lipid Binding ◽  
Peripheral Tissues ◽  
Peptide Receptor ◽  
Pituitary Adenylate Cyclase ◽  
Intestinal Polypeptide

Vasoactive intestinal polypeptide receptor (VIP1R) is a class B G-protein coupled receptor (GPCR) that is widely distributed throughout the central nervous system, T-lymphocytes, and peripheral tissues of organs like lungs and liver. Critical functions of these receptors render them potential pharmacological targets for the treatment of a broad spectrum of inflammatory and neurodegenerative diseases. Here we use atomistic studies to show that phospholipids can act as potent regulators of peptide binding on to the receptor. We simulated the binding of neuropeptide pituitary adenylate cyclase-activating peptide (PACAP27) into the transmembrane bundle of the receptor. The simulations reveal two lipid binding sites on the peptidic ligand for the negatively charged phosphodiester of phospholipids in the extracellular leaflet which lower the peptide-receptor binding free energy by ~8kBT. We further simulated the effect of anionic lipids phosphatidylinositol-4,5-bisphosphate (PIP2). These lipids show much stronger interaction, lowering the peptide-receptor binding energy by an additional ~7kBT compared to POPC lipids. These findings suggest that lipids can play an active role in catalyzing peptide-receptor binding and activating vasoactive intestinal polypeptide receptors.

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