Role of calcium and cAMP in the regulation of rat submandibular mucin secretion

1981 ◽  
Vol 241 (1) ◽  
pp. C76-C85 ◽  
Author(s):  
D. O. Quissell ◽  
K. A. Barzen ◽  
J. L. Lafferty
Keyword(s):  
Adrenergic Receptor ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Calcium Ionophore A23187 ◽  
Secretory Response ◽  
Ionophore A23187 ◽  
Adrenergic Stimulation ◽  
Mucin Secretion ◽  
Mucin Release

The role of cellular adenosine 3',5'-cyclic monophosphate (cAMP) and calcium in the secretion of [14C]glucosamine-labeled mucins by rat submandibular acinar cells was studied. cAMP appeared to be involved, since 1-methyl-3-isobutylxanthine potentiated the secretory response and cellular cAMP levels increased dramatically following adrenergic stimulation. Furthermore, cAMP analogues were able to elicit a secretory response in the absence of beta-adrenergic receptor activation. Cellular calcium was required for mucin secretion at the level of cAMP action; depletion of cellular calcium by pretreatment with EGTA inhibited the secretory response to both adrenergic stimulation and exogenous cAMP addition, but pretreatment with EGTA did not alter the rise in cellular cAMP induced by norepinephrine. Extracellular calcium was not required to elicit mucin secretion, nor could secretion be elicited by means of the calcium ionophore A23187 alone. However, extracellular calcium may have an important biological role in mucin secretion, since cholinergic receptor activation and alpha-adrenergic receptor activation in conjunction with beta-adrenergic receptor activation potentiated mucin release. In addition, the calcium ionophore A23187 potentiated mucin release following cAMP analogue addition.

Inhibitory modulation by cAMP of isoproterenol-induced prostacyclin synthesis in rabbit heart

1989 ◽  
Vol 257 (4) ◽  
pp. R771-R780
Author(s):  
J. L. Williams ◽  
K. U. Malik
Keyword(s):  
Adrenergic Receptor ◽  
Calcium Ionophore ◽  
Phosphodiesterase Inhibitors ◽  
Rabbit Heart ◽  
Receptor Activation ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Enhanced Production

beta-Adrenergic receptor activation in heart is associated with enhanced production of adenosine 3',5'-cyclic monophosphate (cAMP) and prostaglandins (PG). The purpose of the present study was to test the hypothesis that cAMP mediates or modulates PG synthesis elicited by activation of beta-adrenergic receptors in the isolated, perfused rabbit heart. Infusion of 8-(4-chlorophenylthio) (cpt)-cAMP (100 microM), an analogue of cAMP, or stimulation of endogenous cAMP generation with forskolin (2 microM) resulted in a reduction of perfusion pressure and an increase in heart rate and contractility but had no effect on 6-keto-PGF1 alpha output. 6-Keto-PGF1 alpha production elicited by a bolus injection of isoproterenol (Isop) (475 pmol), however, was reduced by greater than 50% in the presence of these agents, cpt-cAMP was also found to inhibit 6-keto-PGF1 alpha output elicited by the calcium ionophore A23187 but not that in response to exogenous arachidonic acid. Perfusion with the adenosine analogue adenylate cyclase inhibitor PIA (1 microM) enhanced by twofold Isop-stimulated output of 6-keto-PGF1 alpha, whereas cAMP accumulation was prevented. Isop-stimulated production of 6-keto-PGF1 alpha was inhibited by 50% in the presence of the phosphodiesterase inhibitors 1-methyl-3-isobutylxanthine (50 microM), Ro 20-1724 (300 microM), or cilostamide (5 microM), whereas both basal and Isop-stimulated cAMP accumulations were enhanced by these agents. These data suggest that cAMP acts as an inhibitory modulator of PG synthesis in response to beta-adrenergic receptor activation in rabbit heart.

Tobacco smoke releases performed mediators from canine mast cells and modulates prostaglandin production

1992 ◽  
Vol 263 (1) ◽  
pp. L67-L72
Author(s):  
P. S. Thomas ◽  
R. E. Schreck ◽  
S. C. Lazarus
Keyword(s):  
Mast Cells ◽  
Tobacco Smoke ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Prostaglandin D2 ◽  
Ionophore A23187 ◽  
Temperature Dependent ◽  
Prostaglandin Production ◽  
Lungs And Airways

The role of an extract of tobacco smoke in activating mast cells was studied. With the use of isolated, canine mast cells as a model, we found that cigarette smoke solution (CSS) induced the release of the performed mediators histamine and tryptase from these cells in an energy- and temperature-dependent, non-cytotoxic manner. There was no requirement for extracellular calcium. Nicotine tartrate did not reproduce the effect of CSS. Interestingly, mast cells produced little prostaglandin D2 (PGD2) in response to the CSS, and there was a concentration-related inhibition of calcium ionophore A23187-induced PGD2 synthesis. This suggests at least two mechanisms acting on the mast cell: tobacco smoke can directly activate mast cells to release performed mediators and can simultaneously inhibit prostaglandin production. These observations suggest a mechanism by which mast cells may participate in the bronchospastic and proinflammatory changes seen in the lungs and airways of smokers.

Leptin is involved in acrosome reaction by facilitating activation of MAPK cascades in the Chinese mitten crab, Eriocheir sinensis

2020 ◽  
Vol 70 (1) ◽  
pp. 81-95
Author(s):  
Qing Li ◽  
Haitao Zhao ◽  
Lin He ◽  
Hongdan Yang ◽  
Qun Wang
Keyword(s):  
Acrosome Reaction ◽  
Calcium Ionophore ◽  
Eriocheir Sinensis ◽  
Calcium Ionophore A23187 ◽  
Mitogen Activated Protein Kinase ◽  
Ionophore A23187 ◽  
Mapk Cascades ◽  
Mitten Crab ◽  
Mitogen Activated Protein

Abstract The role of leptin has been documented in several studies, including activated threonine phosphorylation of extracellular signal-regulated kinase (ERK1/2) in the reproduction of rodents and humans. Our previous studies have demonstrated that mitogen-activated protein kinase (MAPK) cascades ERK, P38, and c-Jun N-terminal kinase (JNK) are involved in the spermatogenesis and acrosome reaction of Eriocheir sinensis. Therefore, the aim of this study was to investigate the expression of leptin and its receptor (LepR), and the effect of leptin on MAPK cascades during calcium ionophore A23187-induced spermatozoa acrosome reaction in crabs. Successful western blotting revealed a 16 kDa band for leptin, and 120 kDa and 90 kDa bands for the obese receptor (LepR), respectively, in the tested male reproductive tissues. Both leptin and LepR were localized at the pro-acrosomal vesicle and apical cap (AC) of spermatids, suggesting their role in the subsequent acrosome reaction. Moreover, acrosome reaction can be enhanced by leptin, and this effect decreased due to the anti-LepR antibody. Afterwards, we investigated the effects of leptin on MAPK cascades. The results showed that leptin mainly activated the phosphorylation of ERK, P38 and JNK proteins in the apical cap during the acrosome reaction in crab spermatozoa. This study addresses the role of leptin on spermatozoa, and suggests that leptin may induce molecular changes associated with spermatozoa during acrosome reaction.

scholarly journals Nitric oxide and peroxynitrite trigger and enhance release of neutrophil extracellular traps

2019 ◽  
Vol 77 (15) ◽  
pp. 3059-3075 ◽  
Author(s):  
Aneta Manda-Handzlik ◽  
Weronika Bystrzycka ◽  
Adrianna Cieloch ◽  
Eliza Glodkowska-Mrowka ◽  
Ewa Jankowska-Steifer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Calcium Ionophore ◽  
Neutrophil Extracellular Traps ◽  
Calcium Ionophore A23187 ◽  
Human Neutrophils ◽  
Ionophore A23187 ◽  
Inflammatory Reactions ◽  
Extracellular Traps

Abstract Despite great interest, the mechanism of neutrophil extracellular traps (NETs) release is not fully understood and some aspects of this process, e.g. the role of reactive nitrogen species (RNS), still remain unclear. Therefore, our aim was to investigate the mechanisms underlying RNS-induced formation of NETs and contribution of RNS to NETs release triggered by various physiological and synthetic stimuli. The involvement of RNS in NETs formation was studied in primary human neutrophils and differentiated human promyelocytic leukemia cells (HL-60 cells). RNS (peroxynitrite and nitric oxide) efficiently induced NETs release and potentiated NETs-inducing properties of platelet activating factor and lipopolysaccharide. RNS-induced NETs formation was independent of autophagy and histone citrullination, but dependent on the activity of phosphoinositide 3-kinases (PI3K) and myeloperoxidase, as well as selective degradation of histones H2A and H2B by neutrophil elastase. Additionally, NADPH oxidase activity was required to release NETs upon stimulation with NO, as shown in NADPH-deficient neutrophils isolated from patients with chronic granulomatous disease. The role of RNS was further supported by increased RNS synthesis upon stimulation of NETs release with phorbol 12-myristate 13-acetate and calcium ionophore A23187. Scavenging or inhibition of RNS formation diminished NETs release triggered by these stimuli while scavenging of peroxynitrite inhibited NO-induced NETs formation. Our data suggest that RNS may act as mediators and inducers of NETs release. These processes are PI3K-dependent and ROS-dependent. Since inflammatory reactions are often accompanied by nitrosative stress and NETs formation, our studies shed a new light on possible mechanisms engaged in various immune-mediated conditions.

Secretory response of dispersed rat submandibular cells. II. Mucin secretion

1980 ◽  
Vol 238 (3) ◽  
pp. C99-C106 ◽  
Author(s):  
D. O. Quissell ◽  
K. A. Barzen
Keyword(s):  
Adrenergic Receptor ◽  
Partial Agonist ◽  
Receptor Activation ◽  
Secretory Response ◽  
Mucin Secretion ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Alpha Adrenergic Receptor ◽  
Median Effective Concentration ◽  
Higher Doses

The secretory response of dispersed rat submandibular cells as it relates to the secretion of D-[1-14C]glucosamine hydrochloride-labeled mucin following sympathomimetic and parasympathomimetic stimulation was evaluated. The adrenergic agonists (-)-norepinephrine and (-)-epinephrine were found to have equal efficacy and potency with a median effective concentration (EC50) of 7.1 x 10(-7) M. (-)-Isoproterenol was found to be acting as a "partial" agonist and had an EC50 of 3.9 x 10(-7) M. (-)-Phenylephrine addition resulted in a small, but significant, secretion of mucin at higher doses tested (10(-4) M--10(-3) M). Neither cholinergic nor alpha-adrenergic receptor stimulation was able to elicit a net increase in the secretion of mucin. However alpha-adrenergic receptor activation in conjunction with beta-adrenergic receptor activation facilitated the rate of secretion. Extracellular Ca2+ and Mg2+ were not required for the secretion of mucin, but extracellular Ca2+ enhanced the rate of secretion following alpha- and beta-adrenergic receptor activation. However extracellular Ca2+ did not enhance mucin secretion following beta-adrenergic receptor activation. Both cellular Ca2+ and beta-adrenergic receptor activation were required to elicit a secretory response following sympathomimetic stimulation.

Inhibitory Effects of Etomidate and Ketamine on Endothelium-dependent Relaxation in Canine Pulmonary Artery

2001 ◽  
Vol 94 (4) ◽  
pp. 668-677 ◽  
Author(s):  
Koji Ogawa ◽  
Satoru Tanaka ◽  
Paul A. Murray
Keyword(s):  
Pulmonary Artery ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Isometric Tension ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Inhibitory Effects ◽  
Pulmonary Arterial ◽  
Synthase Inhibitor ◽  
Endothelium Dependent Relaxation

Background The authors recently demonstrated that acetylcholine-induced pulmonary vasorelaxation had two primary components, nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The goal was to investigate the effects of etomidate and ketamine on the NO- and EDHF-mediated components of pulmonary vasorelaxation in response to acetylcholine, bradykinin, and the calcium ionophore, A23187. Methods Canine pulmonary arterial rings with an intact endothelium were suspended in organ chambers for isometric tension recording. The effects of etomidate and ketamine (10(-5) M and 10(-4) M) on vasorelaxation responses to acetylcholine, bradykinin, and A23187 were assessed in phenylephrine-contracted rings. The NO- and EDHF-mediated components of relaxation were assessed using a NO synthase inhibitor (N-nitro-L-arginine methylester [L-NAME]: 10(-4) M) and a Ca2+-activated potassium channel inhibitor (tetrabutylammonium hydrogen sulfate [TBA]: 10(-3) M) in rings pretreated with a cyclooxygenase inhibitor (ibuprofen: 10(-5) M). Intracellular calcium concentration ([Ca2+]i) was measured in cultured bovine pulmonary artery endothelial cells loaded with acetoxylmethyl ester of fura-2. Results Etomidate and ketamine attenuated pulmonary vasorelaxation in response to acetylcholine and bradykinin, whereas they had no effect on the response to A23187. The relaxant responses to acetylcholine and bradykinin were attenuated by L-NAME or TBA alone and were abolished by combined inhibition in rings pretreated with ibuprofen. Etomidate and ketamine further attenuated both L-NAME-resistant and TBA-resistant relaxation. These anesthetics also inhibited increases in endothelial [Ca2+]i in response to bradykinin, but not A23187. Conclusion These results indicate that etomidate and ketamine attenuated vasorelaxant responses to acetylcholine and bradykinin by inhibiting both NO- and EDHF-mediated components. Moreover, our results suggest that these anesthetics do not directly suppress NO or EDHF activity, but rather inhibit the endothelial [Ca2+]i transient in response to receptor activation.

scholarly journals Regulation of Cardiac L-Type Ca 2+ Channel Ca V 1.2 Via the β-Adrenergic-cAMP-Protein Kinase A Pathway

2013 ◽  
Vol 113 (5) ◽  
pp. 617-631 ◽  
Author(s):  
Sharon Weiss ◽  
Shimrit Oz ◽  
Adva Benmocha ◽  
Nathan Dascal
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Adrenergic Receptor ◽  
Transgenic Animals ◽  
Receptor Activation ◽  
Model Systems ◽  
Adrenergic Stimulation ◽  
New Findings ◽  
Kinase A

In the heart, adrenergic stimulation activates the β-adrenergic receptors coupled to the heterotrimeric stimulatory G s protein, followed by subsequent activation of adenylyl cyclase, elevation of cyclic AMP levels, and protein kinase A (PKA) activation. One of the main targets for PKA modulation is the cardiac L-type Ca 2+ channel (Ca V 1.2) located in the plasma membrane and along the T-tubules, which mediates Ca 2+ entry into cardiomyocytes. β-Adrenergic receptor activation increases the Ca 2+ current via Ca V 1.2 channels and is responsible for the positive ionotropic effect of adrenergic stimulation. Despite decades of research, the molecular mechanism underlying this modulation has not been fully resolved. On the contrary, initial reports of identification of key components in this modulation were later refuted using advanced model systems, especially transgenic animals. Some of the cardinal debated issues include details of specific subunits and residues in Ca V 1.2 phosphorylated by PKA, the nature, extent, and role of post-translational processing of Ca V 1.2, and the role of auxiliary proteins (such as A kinase anchoring proteins) involved in PKA regulation. In addition, the previously proposed crucial role of PKA in modulation of unstimulated Ca 2+ current in the absence of β-adrenergic receptor stimulation and in voltage-dependent facilitation of Ca V 1.2 remains uncertain. Full reconstitution of the β-adrenergic receptor signaling pathway in heterologous expression systems remains an unmet challenge. This review summarizes the past and new findings, the mechanisms proposed and later proven, rejected or disputed, and emphasizes the essential issues that remain unresolved.

Inhibitory Effect of Fentanyl on Acetylcholine-induced Relaxation in Rat Aorta

2004 ◽  
Vol 101 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Ju-Tae Sohn ◽  
Seong-Ho Ok ◽  
Hee-Jin Kim ◽  
Seon-Hak Moon ◽  
Il-Woo Shin ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Response Curve ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Acetylcholine Concentration ◽  
Concentration Response Curve

Background Previous study has shown that fentanyl attenuates acetylcholine-induced vasorelaxation. The goal of the current in vitro study was to identify the muscarinic receptor subtype that is mainly involved in the fentanyl-induced attenuation of endothelium-dependent relaxation elicited by acetylcholine. Methods The effects of fentanyl and muscarinic receptor antagonists on the acetylcholine concentration-response curve were assessed in aortic vascular smooth muscle ring preparations precontracted with phenylephrine. In the rings pretreated independently with pirenzepine, 4-diphenylacetoxyl-N-methylpiperidine methiodide, and naloxone, acetylcholine concentration-response curves were generated in the presence and absence of fentanyl. The effect of fentanyl on the concentration-response curve for calcium ionophore A23187 was assessed. Results Fentanyl (0.297 x 10 0.785 x 10 m) attenuated acetylcholine-induced vasorelaxation in ring preparations with or without 10 m naloxone. Pirenzepine (10 to 10 m) and 4-diphenylacetoxyl-N-methylpiperidine methiodide (10 to 10 m) produced a parallel rightward shift in the acetylcholine concentration-response curve. The concentrations (-log M) of pirenzepine and 4-diphenylacetoxyl-N-methylpiperidine methiodide necessary to displace the concentration-response curve of an acetylcholine by twofold were estimated to be 6.886 +/- 0.070 and 9.256 +/- 0.087, respectively. Methoctramine, 10 m, did not alter the acetylcholine concentration-response curve. Fentanyl, 0.785 x 10 m, attenuated acetylcholine-induced vasorelaxation in the rings pretreated with 10 m pirenzepine but had no effect on vasorelaxation in the rings pretreated with 10 m 4-diphenylacetoxyl-N-methylpiperidine methiodide. Fentanyl, 0.785 x 10 m, did not significantly alter calcium ionophore A23187-induced vasorelaxation. Conclusions These results indicate that fentanyl attenuates acetylcholine-induced vasorelaxation via an inhibitory effect at a level proximal to nitric oxide synthase activation on the pathway involving endothelial M3 muscarinic receptor activation in rat aorta.

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