The Ca(2+) and cAMP/PKA pathways are the primary signaling systems in secretory epithelia that control virtually all secretory gland functions. Interaction and crosstalk in Ca(2+) and cAMP signaling occur at multiple levels to control and tune the activity of each other. Physiologically, Ca(2+) and cAMP signaling operate at 5-10% of maximal strength, but synergize to generate the maximal response. Although synergistic action of the Ca(2+) and cAMP signaling is the common mode of signaling and has been known for many years, we know very little of the molecular mechanism and mediators of the synergism. In this review, we discuss crosstalk between the Ca(2+) and cAMP signaling and the function of IRBIT (IP3 receptors binding protein release with IP3) as a third messenger that mediates the synergistic action of the Ca(2+) and cAMP signaling.
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http://dx.doi.org/10.1016/j.ceca.2014.01.006 | DOI Listing |
Behav Brain Res
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007. Electronic address:
The astroglial glutamate transporter in the hippocampus and anterior cingulate cortex (ACC) is critically involved in chronic pain-induced cognitive and psychiatric abnormalities. We have previously reported that LDN-212320, a glutamate transporter-1 (GLT-1) activator, attenuates complete Freund's adjuvant (CFA)-induced acute and chronic nociceptive pain. However, the cellular and molecular mechanisms underlying GLT-1 modulation in the hippocampus and ACC during chronic pain-induced cognitive deficit-like and anxiety-like behaviors remain unknown.
View Article and Find Full Text PDFFunction (Oxf)
January 2025
Institute for Integrative Physiology, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL. 60637, USA.
Patients with obstructive sleep apnea (OSA) experience chronic intermittent hypoxia (CIH). OSA patients and CIH-treated rodents exhibit overactive sympathetic nervous system and hypertension, mediated through hyperactive carotid body (CB) chemoreflex. Activation of olfactory receptor 78 (Olfr78) by hydrogen sulfide (H2S) is implicated in CB activation and sympathetic nerve responses to CIH, but the downstream signaling pathways remain unknown.
View Article and Find Full Text PDFJ Cell Sci
January 2025
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
G protein-coupled receptor (GPCR) signalling pathways underlie numerous physiological processes, are implicated in many diseases and are major targets for therapeutics. There are more than 800 GPCRs, which together transduce a vast array of extracellular stimuli into a variety of intracellular signals via heterotrimeric G protein activation and multiple downstream effectors. A key challenge in cell biology research and the pharmaceutical industry is developing tools that enable the quantitative investigation of GPCR signalling pathways to gain mechanistic insights into the varied cellular functions and pharmacology of GPCRs.
View Article and Find Full Text PDFCell Commun Signal
January 2025
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Background: Bok is a poorly characterized Bcl-2 protein family member with roles yet to be clearly defined. It is clear, however, that Bok binds strongly to inositol 1,4,5-trisphosphate (IP) receptors (IPRs), which govern the mobilization of Ca from the endoplasmic reticulum, a signaling pathway required for many cellular processes. Also known is that Bok has a highly conserved phosphorylation site for cAMP-dependent protein kinase at serine-8 (Ser-8).
View Article and Find Full Text PDFReprod Biol
January 2025
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:
Contrary to the evidence supporting the role for insulin in stimulating uterine contraction, only a limited number of studies have highlighted the inhibitory effect of insulin on myometrial contractions in human and rodent. A hypothetical narrative review of the current literature was conducted, revealing the current literature and shows the potential inhibitory effects of insulin on myometrial contractility. These inhibitory mechanisms include activation of adenylyl cyclase signaling pathways, an increase in cAMP production, a decrease in Ca influx and cytosolic Ca, hyperpolarization of the cell membrane, and stimulation of NO synthesis.
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