Alpha-Adrenergic Agonists Stimulate Fluid Secretion in Lacrimal Gland Ducts

Szarka, Dóra; Elekes, Gréta; Berczeli, Orsolya; Vizvári, Eszter; Szalay, L.; Ding, Chuanqing; Tálosi, László; Tóth-Molnár, Edit

doi:10.1167/iovs.61.14.3

Cited by 7 publications

(7 citation statements)

References 21 publications

(41 reference statements)

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“…Besides the apparent role of parasympathetic agonists, a substantial outcome of α-adrenergic activation on LG ductal secretion was also proven in our previous experiments. 10 To assess the role of AQP4 in the α-adrenergic stimulation-induced fluid secretion, PHE (10 µM) was applied. Although PHE induced a relevant secretory response in both WT and KO ducts, this response was significantly lower in ducts isolated from AQP4 KO LGs (WT = 274 ± 63 pl/min/mm 2 and AQP4 KO = 158 ± 53 pl/min/mm 2 , respectively, P = 0.006; Fig.…”

Section: Resultsmentioning

confidence: 99%

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The Role of Aquaporin 4 in Lacrimal Gland Ductal Fluid Secretion in Mice

Elekes,

Csapó,

Szarka

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose Earlier reports highlighted the predominant presence of aquaporin 4 (AQP4) in the duct cells of rabbit lacrimal glands (LGs). Whereas significant alterations in AQP4 mRNA levels have been observed in experimental dry eye and during pregnancy, the impact of AQP4 in LG ductal fluid production remains unclear. In our recent work, the role of AQP4 in LG ductal fluid secretion was investigated utilizing wild type (WT) and AQP4 knock out (KO) mice. Methods Tear production was assessed in both WT and KO animals. Immunostaining was used to identify AQP4 protein. Duct segments were harvested from LGs of WT and KO mice. Fluid secretion and filtration permeability (P f ) were quantified using video-microscopy. Ductal tear production, elicited by a cell-permeable cAMP analogue (8-bromo cAMP), carbachol, vasoactive intestinal peptide (VIP), and phenylephrine (PHE), were assessed in both WT and KO ducts. Results A higher expression of AQP4 protein was noted in the duct cells from WT mice when compared to acinar cells. P f did not show notable alterations between WT and AQP4 KO ducts. Carbachol elicited comparable secretory responses in ducts from both WT and KO animals. However, 8-bromo cAMP, VIP, and PHE stimulation resulted in decreased secretion in ducts from AQP4 KO LGs. Conclusions Our findings underscore the functional relevance of AQP4 in the fluid production of mouse LG ducts. AQP4 seems to play different roles in fluid secretions elicited by different secretagogues. Specifically, cAMP-mediated, and adrenergic agonist-related secretions were reduced in AQP4 KO ducts.

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Section: Resultsmentioning

confidence: 99%

“… 8 , 9 Autonomic regulation of ductal function has also been investigated. 10 These accumulating experimental results provide compelling evidence that ductal cells possess an essential, albeit species-dependent function in the formation of the final secreta of the LG. 11 …”

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confidence: 97%

The Role of Aquaporin 4 in Lacrimal Gland Ductal Fluid Secretion in Mice

Elekes,

Csapó,

Szarka

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…It is clear that, through dynamic modulations of its lipid environment and associated proteins, the ER–PM contact site plays a huge regulatory role on the spatiotemporal activity of the versatile second messengers Ca 2+ and cAMP. Therefore, a better understanding of this complex regulation may also reveal unknown aspects of crucial cell functions, such as ion and fluid secretion [ 273 , 274 , 275 , 276 , 277 , 278 ]. However, as we only start to appreciate its complexity, many open questions still need to be addressed.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling

Crul

Maléth

2021

IJMS

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In eukaryotic cells, ultimate specificity in activation and action—for example, by means of second messengers—of the myriad of signaling cascades is primordial. In fact, versatile and ubiquitous second messengers, such as calcium (Ca2+) and cyclic adenosine monophosphate (cAMP), regulate multiple—sometimes opposite—cellular functions in a specific spatiotemporal manner. Cells achieve this through segregation of the initiators and modulators to specific plasma membrane (PM) subdomains, such as lipid rafts and caveolae, as well as by dynamic close contacts between the endoplasmic reticulum (ER) membrane and other intracellular organelles, including the PM. Especially, these membrane contact sites (MCSs) are currently receiving a lot of attention as their large influence on cell signaling regulation and cell physiology is increasingly appreciated. Depletion of ER Ca2+ stores activates ER membrane STIM proteins, which activate PM-residing Orai and TRPC Ca2+ channels at ER–PM contact sites. Within the MCS, Ca2+ fluxes relay to cAMP signaling through highly interconnected networks. However, the precise mechanisms of MCS formation and the influence of their dynamic lipid environment on their functional maintenance are not completely understood. The current review aims to provide an overview of our current understanding and to identify open questions of the field.

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“…This subject has also revealed the intricacies of assessments involving the bipolar issue. In addition, it was observed that the thickness of the alpha2-AR was enhanced in the platelets patients' who had bipolar disorder [38] (2) Beta2-Adrenergic Receptors. Studies on the quantities of beta2-adrenergic receptors in peripheral cells, however, have shown inconsistent outcomes, with one finding being that depressed individuals' leukocytes have lower levels of beta-AR-stimulated AC activity [39,40,41,42].…”

Section: Studies On Peripheral Blood Cellsmentioning

confidence: 99%

Section: Gpcrs and Mood Disordersmentioning

confidence: 99%

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

Rahman

Islam

Mim

et al. 2022

Oxidative Medicine and Cellular Longevity

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G protein-coupled receptors (GPCRs) are intricately involved in the conversion of extracellular feedback to intracellular responses. These specialized receptors possess a crucial role in neurological and psychiatric disorders. Most nonsensory GPCRs are active in almost 90% of complex brain functions. At the time of receptor phosphorylation, a GPCR pathway is essentially activated through a G protein signaling mechanism via a G protein-coupled receptor kinase (GRK). Dopamine, an important neurotransmitter, is primarily involved in the pathophysiology of several CNS disorders; for instance, bipolar disorder, schizophrenia, Parkinson’s disease, and ADHD. Since dopamine, acetylcholine, and glutamate are potent neuropharmacological targets, dopamine itself has potential therapeutic effects in several CNS disorders. GPCRs essentially regulate brain functions by modulating downstream signaling pathways. GPR6, GPR52, and GPR8 are termed orphan GPCRs because they colocalize with dopamine D1 and D2 receptors in neurons of the basal ganglia, either alone or with both receptors. Among the orphan GPCRs, the GPR52 is recognized for being an effective psychiatric receptor. Various antipsychotics like aripiprazole and quetiapine mainly target GPCRs to exert their actions. One of the most important parts of signal transduction is the regulation of G protein signaling (RGS). These substances inhibit the activation of the G protein that initiates GPCR signaling. Developing a combination of RGS inhibitors with GPCR agonists may prove to have promising therapeutic potential. Indeed, several recent studies have suggested that GPCRs represent potentially valuable therapeutic targets for various psychiatric disorders. Molecular biology and genetically modified animal model studies recommend that these enriched GPCRs may also act as potential therapeutic psychoreceptors. Neurotransmitter and neuropeptide GPCR malfunction in the frontal cortex and limbic-related regions, including the hippocampus, hypothalamus, and brainstem, is likely responsible for the complex clinical picture that includes cognitive, perceptual, emotional, and motor symptoms. G protein and GPCR-mediated signaling play a critical role in developing new treatment options for mental health issues, and this study is aimed at offering a thorough picture of that involvement. For patients who are resistant to current therapies, the development of new drugs that target GPCR signaling cascades remains an interesting possibility. These discoveries might serve as a fresh foundation for the creation of creative methods for pharmacologically useful modulation of GPCR function.

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Alpha-Adrenergic Agonists Stimulate Fluid Secretion in Lacrimal Gland Ducts

Cited by 7 publications

References 21 publications

The Role of Aquaporin 4 in Lacrimal Gland Ductal Fluid Secretion in Mice

The Role of Aquaporin 4 in Lacrimal Gland Ductal Fluid Secretion in Mice

Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

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