ArticleInvestigative ophthalmology & visual science2005
Nitric oxide and cGMP mediate alpha1D-adrenergic receptor-Stimulated protein secretion and p42/p44 MAPK activation in rat lacrimal gland.
Article in Investigative ophthalmology & visual science, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- A gatekeeper sympathetic control of lacrimal tear secretion and dry eye onset through the NA-Adra1a-Ucp2 pathway.Nature communications · 2025Article
- α1D Adrenergic Receptor Antagonism Protects Against High Glucose-Induced Mitochondrial Dysfunction and Blood Retinal Barrier Breakdown in ARPE-19 Cells.International journal of molecular sciences · 2025Article
- Adrenoceptors in the Eye - Physiological and Pathophysiological Relevance.Handbook of experimental pharmacology · 2024Review
- Oxidative Stress in the Protection and Injury of the Lacrimal Gland and the Ocular Surface: are There Perspectives for Therapeutics?Frontiers in cell and developmental biology · 2022Review
- Phenylephrine increases tear cathepsin S secretion in healthy murine lacrimal gland acinar cells through an alternative secretory pathway.Experimental eye research · 2021Article
- Alpha-Adrenergic Agonists Stimulate Fluid Secretion in Lacrimal Gland Ducts.Investigative ophthalmology & visual science · 2020Article
- TFOS DEWS II pain and sensation report.The ocular surface · 2017Review
- Signaling Pathways of Purinergic Receptors and Their Interactions with Cholinergic and Adrenergic Pathways in the Lacrimal Gland.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2016Review
- Interaction of alpha1D-adrenergic and P2X(7) receptors in the rat lacrimal gland and the effect on intracellular [Ca2+] and protein secretion.Investigative ophthalmology & visual science · 2011Article
- Cholinergic agonists activate P2X7 receptors to stimulate protein secretion by the rat lacrimal gland.Investigative ophthalmology & visual science · 2011Article
- Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells.Naunyn-Schmiedeberg's archives of pharmacology · 2010Article
- Characterization of P2X7 purinergic receptors and their function in rat lacrimal gland.Investigative ophthalmology & visual science · 2009Article
- Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases.Progress in retinal and eye research · 2009Review
- The aging lacrimal gland: changes in structure and function.The ocular surface · 2008Review
- Effects of alpha1D-adrenergic receptors on shedding of biologically active EGF in freshly isolated lacrimal gland epithelial cells.American journal of physiology. Cell physiology · 2006Article
- In vivo studies on the effects of alpha1-adrenoceptor antagonists on pupil diameter and urethral tone in rabbits.Naunyn-Schmiedeberg's archives of pharmacology · 2006Article
- Role of protein kinase C in cholinergic stimulation of lacrimal gland protein secretion.FEBS letters · 1994Article
- Activation of latent transforming growth factor-beta1 by nitric oxide in macrophages: role of soluble guanylate cyclase and MAP kinases.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair SocietyArticle
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo determine whether alpha(1)-adrenergic receptors use the nitric oxide (NO)/cGMP pathway to stimulate protein secretion by rat lacrimal gland.
methodsIdentification and cellular location of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) were determined by Western blot and immunofluorescence techniques, respectively. Rat lacrimal gland acini were isolated by collagenase digestion, and protein secretion stimulated by phenylephrine, an alpha(1)-adrenergic agonist, was measured with a fluorescence assay system. Acini were preincubated with inhibitors for 20 minutes before addition of phenylephrine (10(-4) M). NO and cGMP were measured in response to phenylephrine stimulation. Activation of p42/p44 MAPK was determined by Western blot analysis with an antibody against phosphorylated (active) p42/p44 MAPK.
resultseNOS and nNOS were both present in lacrimal gland. eNOS appeared to be localized with caveolae, whereas nNOS was present in the nerves surrounding the acini. Inhibition of eNOS with N(G)-nitro-l-arginine methyl ester (l-NAME; 10(-6) M) completely inhibited phenylephrine-stimulated protein secretion, whereas the inactive isomer d-NAME and inhibition of nNOS with S-methyl-l-thiocitrulline did not. Phenylephrine increased NO production in a time- and concentration-dependent manner, but the increase was abolished by the alpha(1D)-adrenergic receptor inhibitor BMY-7378. Inhibition of guanylate cyclase with oxadiazoloquinoxalin (ODQ) also inhibited phenylephrine-induced protein secretion, whereas phenylephrine caused a 2.2-fold increase in cGMP. In addition, preincubation with l-NAME and ODQ inhibited phenylephrine-stimulated p42/p44 MAPK activation.
conclusionsalpha(1D)-Adrenergic agonists stimulate eNOS to produce NO, leading to production of cGMP by guanylate cyclase, to transduce the extracellular signal through the cell and stimulate protein secretion in rat lacrimal gland.
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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.