Cholinergic potentiation of isoproterenol-induced cAMP level in sweat gland

1983 ◽  
Vol 245 (3) ◽  
pp. C189-C195 ◽  
Author(s):  
K. Sato ◽  
F. Sato
Keyword(s):  
Camp Level ◽  
Sweat Glands ◽  
Maximal Response ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Camp Accumulation ◽  
Major Mechanism ◽  
Agonist Concentration ◽  
Dose Dependent ◽  
Eccrine Sweat Glands

Although methacholine (MCh) and a Ca2+ ionophore A23187 do not enhance the tissue adenosine 3',5'-cyclic monophosphate (cAMP) level by themselves, they markedly potentiate isoproterenol (ISO)-induced tissue cAMP accumulation in isolated simian eccrine sweat glands in a dose-dependent manner. The agonist concentration producing 50% of the maximal response of such a potentiated cAMP accumulation was 2.1 X 10(-7) M for MCh, 2.5 X 10(-7) M for ISO, and 2.9 X 10(-6) M for A23187. Unlike cAMP accumulation induced by ISO alone, MCh-stimulated ISO-induced cAMP accumulation is dependent on extracellular Ca2+. MCh- plus ISO-induced cAMP level is tripled by 10(-2) M theophylline (TH), and while the ISO-induced cAMP level was also elevated by TH, it was not enhanced to the level of ISO-plus MCh-induced cAMP accumulation, indicating that phosphodiesterase inhibition is not the major mechanism for the augmentative effect of MCh. The augmentative effect of MCh was seen only in the secretory portion, whereas that of A23187 was seen in both the secretory portion and the duct. The data suggest that MCh-induced augmentation of ISO-stimulated cAMP accumulation is due to increased cAMP formation, not decreased cAMP degradation, and that it may be mediated by an elevated intracellular Ca2+.

Effect of VIP on sweat secretion and cAMP accumulation in isolated simian eccrine glands

1987 ◽  
Vol 253 (6) ◽  
pp. R935-R941 ◽  
Author(s):  
K. Sato ◽  
F. Sato
Keyword(s):  
Functional Significance ◽  
Time Course ◽  
Sweat Rate ◽  
Camp Level ◽  
Sweat Glands ◽  
Camp Accumulation ◽  
Eccrine Glands ◽  
Sweat Secretion ◽  
Eccrine Sweat Glands ◽  
Eccrine Sweat

Although vasoactive intestinal peptide (VIP)-immunoreactive nerves have been identified around the eccrine sweat glands, their functional significance is unknown. We found that VIP evokes eccrine sweat secretion in isolated monkey palm eccrine sweat glands in vitro as profusely as does isoproterenol (Iso), however, at concentrations two orders of magnitude lower than that of Iso. Like Iso sweating, the VIP sweating was relatively insensitive to removal of Ca2+ from the medium. The time course of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in the secretory coil paralleled that of sweat secretion. However, unlike Iso stimulations, both VIP-induced cAMP level and VIP sweat rate markedly declined with time. The attenuation of VIP sweat rate was reversed by forskolin and by theophylline, suggesting that the attenuation is caused partially by desensitization of the receptor-cyclase complex and/or by cAMP breakdown by phosphodiesterase. Forskolin stimulated the VIP-induced cAMP level more than can be expected from a simple additive effect. The sudorific effects of a submaximal concentration of VIP (6 X 10(-9) M) and that of methacholine (MCh) (10(-8) M) were only additive. The VIP-induced cAMP level was markedly augmented by MCh and further enhanced by Iso with or without theophylline. Thus the most salient biochemical consequence of the VIP-ergic component of sweat gland innervation is to induce synergistic amplification of tissue cAMP accumulation. The functional significance of synergistically accumulated cAMP in physiological eccrine sweating remains to be studied.

Endothelium-dependent and -independent relaxations to adenosine in guinea pig aorta

1990 ◽  
Vol 259 (1) ◽  
pp. H62-H67 ◽  
Author(s):  
J. P. Headrick ◽  
R. M. Berne
Keyword(s):  
Guinea Pig ◽  
Sodium Nitroprusside ◽  
Maximal Response ◽  
Dependent Manner ◽  
Prostaglandin F2 Alpha ◽  
Endothelial Response ◽  
Alpha Response ◽  
Dose Dependent ◽  
Subtype 3 ◽  
Indomethacin Treatment

Effects of endothelial removal and hypoxia on responses to adenosine, 5'-(N-ethylcarboxamido)-adenosine (NECA), 2-chloroadenosine, N6-cyclohexyladenosine (CHA), sodium nitroprusside, and acetylcholine were examined in guinea pig aortic rings. Rings contracted with 2 microM prostaglandin F2 alpha (PGF2 alpha) relaxed in a dose-dependent manner in response to all drugs. The order of potency of adenosine compounds was NECA greater than 2-chloroadenosine greater than adenosine greater than CHA. Endothelial rubbing potentiated the PGF2 alpha response by 11 +/- 3%, eliminated the acetylcholine (ACh) response, but had no effect on nitroprusside and CHA responses. Responses to adenosine, NECA, and 2-chloroadenosine were significantly depressed by rubbing (P less than 0.05). Oxyhemoglobin (5 microM) and metyrapone (0.1 mM) reduced ACh responses in intact rings but had no effect on the adenosine and nitroprusside responses. Indomethacin treatment (10 microM) did not alter ACh, nitroprusside, or adenosine responses in intact rings. Hypoxia (10% O2) potentiated maximal responses to adenosine (+26 +/- 3%) and nitroprusside (+28 +/- 4%) in intact and rubbed rings and reduced the maximal response to ACh in intact rings (-28 +/- 3%). It is concluded that 1) adenosine mediates relaxation in guinea pig aorta by endothelial-dependent and -independent mechanisms, 2) receptors involved in both endothelial-dependent and -independent relaxations are characteristic of the A2 adenosine subtype, 3) the endothelial response appears unrelated to EDRF or prostanoid release, and 4) the adenosine response is significantly potentiated by hypoxia.

scholarly journals Biochanin A, the Most Potent of 16 Isoflavones, Induces Relaxation of the Coronary Artery Through the Calcium Channel and cGMP-dependent Pathway

Planta Medica ◽  
2020 ◽  
Vol 86 (10) ◽  
pp. 708-716
Author(s):  
Thomas Migkos ◽  
Jana Pourová ◽  
Marie Vopršalová ◽  
Cyril Auger ◽  
Valérie Schini-Kerth ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Mechanism Of Action ◽  
Biochanin A ◽  
Dependent Manner ◽  
Major Mechanism ◽  
Camp Pathway ◽  
Clinical Interest ◽  
Series Of Experiments ◽  
Dose Dependent ◽  
Dependent Pathway

AbstractThe dietary intake of flavonoids seems to be inversely related to cardiovascular mortality. The consumption of isoflavonoids is increasing in the general population, especially due to the use of food supplements and a variety of isoflavonoid-rich foods. However, detailed studies on the vascular influence of individual pure isoflavonoids are mostly missing. For this study, 16 isoflavonoids were initially screened for their vasorelaxant properties on rat aortas. The 2 most potent of them, biochanin A and glycitein, were further tested for the mechanism of action on porcine coronary arteries. They both induced an endothelium independent vascular relaxation, with EC50 below 6 and 17 µM, respectively. Biochanin A, but not glycitein, was able to block the vasoconstriction caused by KCl, CaCl2, serotonin, and U46619 in a dose-dependent manner. Another series of experiments suggested that the major mechanism of action of biochanin A was the inhibition of L-type calcium channels. Moreover, biochanin A in relatively small concentrations (2 – 4 µM) interfered with the cGMP, but not cAMP, pathway in isolated coronary arteries. These results indicate that some isoflavonoids, in particular biochanin A, are able to have vasodilatory effects in micromolar concentrations, which is of potential clinical interest for the management of cardiovascular pathologies.

Thyroid-stimulating activity of human chorionic gonadotropin in sera of normal pregnant women

1990 ◽  
Vol 123 (3) ◽  
pp. 277-281 ◽  
Author(s):  
Masayoshi Yoshimura ◽  
Mitsushige Nishikawa ◽  
Masateru Horimoto ◽  
Norio Yoshikawa ◽  
Susumu Sawaragi ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Dependent Manner ◽  
Camp Accumulation ◽  
Serum Samples ◽  
Adenylate Cyclase Activation ◽  
Thyrotropic Activity ◽  
Camp Levels ◽  
Dose Dependent

Abstract. To ascertain the thyrotropic activity of human chorionic gonadotropin in sera of normal pregnant women, we examined the adenylate cyclase activation in the cultured FRTL-5 cells by extracted hCG from 7 normal pregnant women. hCG was extracted from the sera using anti-hCG-β subunit monoclonal antibodycoated microwells, eluted with 2 mol/l guanidine-HCl, and reconstituted with hypotonic Hanks' solution. FRTL-5 cells were precultured in 5H medium, incubated for 2 h with the serum extracts, and the cAMP released into the medium was measured. hCG levels in serum extracts ranged from 1100 to 6800 IU/l; values corresponded to 1.4-19.8% compared with those in the original serum samples. Addition of the extracts to FRTL-5 cells resulted in significant increases in the cAMP accumulation, ranging from 9.8 to 59.0 nmol/l. cAMP levels were also increased in a dose-dependent manner by adding purified hCG as well as crude hCG and hTSH to FRTL-5 cells. These findings suggest that the thyroid gland of normal pregnant women may actually be stimulated by hCG itself.

Cyclic GMP accumulation during cholinergic stimulation of eccrine sweat glands

1984 ◽  
Vol 247 (3) ◽  
pp. C234-C239 ◽  
Author(s):  
K. Sato ◽  
F. Sato
Keyword(s):  
Time Course ◽  
Sweat Glands ◽  
Cgmp Level ◽  
Ionophore A23187 ◽  
Cholinergic Stimulation ◽  
Sweat Secretion ◽  
Transient Elevation ◽  
Eccrine Sweat Glands ◽  
Eccrine Sweat

The possibility that guanosine 3'5'-cyclic monophosphate (cGMP) may be an intracellular mediator of cholinergic stimulation [methacholine chloride (MCh)] was explored by comparing the relationship between the time course of cGMP accumulation and sweat secretion by use of isolated monkey palm eccrine sweat glands. Isolated sweat glands were incubated with MCh or other agents, and tissue levels of cGMP were determined by radioimmunoassay. In parallel experiments, sweat secretion was induced from cannulated single sweat glands in vitro. Stimulation with MCh produced a Ca-dependent transient elevation of cGMP level from 10 to 80 fmol/gland, peaking at 1-2 min but returning to the basal level by 5 min. The MCh-induced cGMP level was dose dependent and was inhibited by atropine. Ionophore A23187 (2 X 10(-4) M), however, caused persistent elevation of cGMP level for at least 20 min. Neither 10(-4) M MNNG, which elevated the cGMP level comparably with MCh stimulation, nor 8-bromo-cGMP (2 mM) induced sweat secretion. Thus although a parallelism between the cGMP level and sweating rate appears to hold for the initial stage of MCh-induced sweating, it does not hold for the steady state of sweat secretion. Data could not be interpreted to favor the notion that cGMP may be the intracellular mediator of cholinergic sweat secretion.

Gastrin and carbachol require cAMP to elicit aminopyrine accumulation in isolated pig and rat parietal cells

1995 ◽  
Vol 268 (1) ◽  
pp. G82-G89 ◽  
Author(s):  
Z. Q. Li ◽  
J. L. Cabero ◽  
S. Mardh
Keyword(s):  
Mechanisms Of Action ◽  
Camp Level ◽  
Parietal Cells ◽  
Dependent Manner ◽  
Camp Content ◽  
Camp Analogue ◽  
S 100 ◽  
Camp Levels ◽  
Dose Dependent

The role of endogenous adenosine 3',5'-cyclic monophosphate (cAMP) in the mechanisms of action of gastrin and carbachol on aminopyrine accumulation in isolated pig and rat parietal cells was investigated. In pig cells, pentagastrin (100 nM) alone stimulated aminopyrine accumulation, an action significantly reduced by the protein kinase A inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMP[S]; 100 microM). In rat cells, gastrin-17 (100 nM) was incapable of stimulating aminopyrine accumulation, but it potentiated the action of histamine (100 microM). Carbachol (10 microM) stimulated aminopyrine accumulation and potentiated the action of histamine, and its action was potentiated in a dose-dependent manner by Sp-adenosine 3',5'-cyclic monophosphothioate (Sp-cAMP[S]; a cAMP analogue) in both species. The effect of carbachol was dose dependently reduced by Rp-cAMP[S]. The basal cAMP in pig parietal cells was 3.5-fold higher than that in rat parietal cells. Histamine (100 microM) and 3-isobutyl-1-methylxanthine (IBMX; 100 microM) only slightly elevated the cAMP content (1.2- to 2.9-fold the basal level) in both pig and rat parietal cells. Their combination, however, increased the cAMP level by 8- to 38-fold, but it did not increase aminopyrine accumulation above that elicited by histamine alone. Gastrin did not alter the cAMP levels in parietal cells of either of the two species. Both gastrin and carbachol increased cytosolic free Ca2+ in enriched pig and rat parietal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of the endogenous intestinal peptide that stimulates the rectal gland of Scyliorhinus canicula

1995 ◽  
Vol 268 (6) ◽  
pp. R1359-R1364 ◽  
Author(s):  
W. G. Anderson ◽  
J. M. Conlon ◽  
N. Hazon
Keyword(s):  
High Performance ◽  
Squalus Acanthias ◽  
Gland Secretion ◽  
Rectal Gland ◽  
Maximal Response ◽  
Dependent Manner ◽  
Gut Peptides ◽  
Scyliorhinus Canicula ◽  
Dose Dependent

It has been postulated that gut peptides play a major role in the regulation of rectal gland secretion in elasmobranchs. An isolated perfused rectal gland secretion in elasmobranchs. An isolated perfused rectal gland preparation was developed for Scyliorhinus canicula that responded to dibutyryl 3',5'-cyclic monophosphate plus 3-isobutyl-1-methylxanthine, increasing chloride clearance rates threefold over basal levels. Activity was stimulated by an endogenous peptide, isolated in pur form by reverse-phase high-performance liquid chromatography from the intestine of S. canicula. The primary structure was established as Ser-Pro-Ser-Asn-Ser-Lys-Cys-Pro-Asp-Gly-Pro-Asp-Cys-Phe-Val-Gly-Leu-Met- NH2. This is a sequence identical to that of the tachykinin scyliorhinin II. Perfusion of synthetic scyliorhinin II increased secretion rate in the rectal gland of S. canicula in a dose-dependent manner with a maximal response at 10(-6) M, whereas vasoactive intestinal peptide, a stimulator in the spiny dogfish, Squalus acanthias, had no effect. We propose that scyliorhinin II is the uncharacterized peptide rectin, previously identified from the intestine of S. canicula.

The role of intracellular Ca2+ during early sexual development in Dictyostelium discoideum: effects of LaCl3, LaCl3, Ins(1,4,5)P3, TMB-8, chlortetracycline and A23187 on cell fusion

1988 ◽  
Vol 90 (3) ◽  
pp. 465-473 ◽  
Author(s):  
MICHAEL A. LYDAN ◽  
DANTON H. O'DAY
Keyword(s):  
Dictyostelium Discoideum ◽  
Cell Fusion ◽  
Calcium Release ◽  
Cytosolic Calcium ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Extracellular Environment ◽  
Internal Calcium

The agents LaCl3, Ins(1,4,5)P3, TMB-8, chlortetracycline (CTC) and A23187 were used to study the requirement for internal calcium mobilization during gamete cell fusion in Dictyostelium discoideum. The inhibition of the influx of calcium (LaCl3) prevented cell fusion in a dose-dependent manner. At the intracellular level, Ins(1,4,5)P3, an endogenous regulator of calcium release from intracellular stores, stimulated cell fusion within one hour following its addition. Treatment with agents that prevent the release of calcium from intracellular stores (TMB-8, CTC) also inhibited cell fusion in a dose-dependent manner. However, the non-specific augmentation of cytosolic calcium levels through the use of the ionophore A23187 inhibited cell fusion, and the amount inhibition was directly related to the drug concentration. Studies on cell morphology and growth plus results from reversibility experiments involving the ability to form macrocysts reveal that these effects are not due to non-specific drug toxicity. In total, these results suggest that the mobilization of calcium both from the extracellular environment and from intracellular stores important and is probably regulated during gamete cell fusion in D. discoideum.

A2 Adenosine Receptors Inhibit Calcium Influx Through L-Type Calcium Channels in Rod Photoreceptors of the Salamander Retina

2002 ◽  
Vol 87 (1) ◽  
pp. 351-360 ◽  
Author(s):  
Salvatore L. Stella ◽  
Eric J. Bryson ◽  
Wallace B. Thoreson
Keyword(s):  
Calcium Influx ◽  
Glutamate Release ◽  
Dependent Manner ◽  
Rod Photoreceptors ◽  
Major Mechanism ◽  
Intracellular Ca ◽  
Selective Agonists ◽  
Dose Dependent ◽  
Isolated Cell ◽  
A2 Adenosine Receptors

Presynaptic inhibition is a major mechanism for regulating synaptic transmission in the CNS and adenosine inhibits Ca2+ currents ( I Ca) to reduce transmitter release at several synapses. Rod photoreceptors possess L-type Ca2+ channels that regulate the release ofl-glutamate. In the retina, adenosine is released in the dark when l-glutamate release is maximal. We tested whether adenosine inhibits I Ca and intracellular Ca2+ increases in rod photoreceptors in retinal slice and isolated cell preparations. Adenosine inhibited both I Ca and the [Ca2+]i increase evoked by depolarization in a dose-dependent manner with ∼25% inhibition at 50 μM. An A2-selective agonist, ( N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) (DPMA), but not the A1- or A3-selective agonists, ( R)- N 6-(1-methyl-2-phenylethyl)adenosine and N 6-2-(4-aminophenyl)ethyladenosine, also inhibited I Ca and depolarization-induced [Ca2+]iincreases. An inhibitor of protein kinase A (PKA), Rp-cAMPS, blocked the effects of DPMA on both I Ca and the depolarization-evoked [Ca2+]i increase in rods. The results suggest that activation of A2receptors stimulates PKA to inhibit L-type Ca2+channels in rods resulting in a decreased Ca2+influx that should suppress glutamate release.

Cyclic AMP-Dependent Protein Kinase Mediates Glycoprotein Ibα Shedding from Platelet.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3653-3653
Author(s):  
Kesheng Dai ◽  
Rong Yan ◽  
Hong Cheng ◽  
Richard Bodnar ◽  
Changgeng Ruan
Keyword(s):  
Protein Kinase ◽  
Platelet Activation ◽  
Calcium Ionophore ◽  
Platelet Glycoprotein ◽  
Calpain Inhibitor ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Dose Dependent

Abstract Extracellular domain of platelet glycoprotein (GP) Ibα contains ligand binding sites for von Willebrand factor (VWF) and α-thrombin. GPIbα binding to VWF exposed at the injured vessel initiates thrombus formation, thus it plays key roles in thrombosis and hemostasis. While a lot of research has been performed to elucidate the critical roles for GPIbα in platelet activation, little is known about the negative regulatory mechanisms of this adhesion receptor. Here we show that inhibition of cAMP-dependent protein kinase (PKA) resulted in the shedding of GPIbα from platelet. GPIbα was shed after platelets were incubated with PKA inhibitors (H89, PKI) in a dose-dependent manner. PKA mediated GPIbα shedding was inhibited by calpain inhibitors (MDL 28170, E64d, calpain inhibitor-I, calpain inhibitor-II) in a dose-dependent manor, suggesting that shedding of GPIbα is a result of calpain cleavage. Time course experiment revealed that PKA mediated GPIbα shedding occurred as a late event, 10 minutes after platelet activation. Flow cytometry and western-blot data suggested that the cleavage site was at N-terminal of residues 484 and 485 on GPIbα. These residues are responsible for disulfide bond linkage to GPIbβ. Though the size of GPIbα shed fragments from platelet treated with H89 was the same as platelet treated with calcium ionophore A23187 or thrombin, yet the intensity of platelet activation, the amount of GPIbα shedding, and redistribution of GPIbα were different, suggesting that the mechanism of PKA inhibition-initiated GPIbα shedding is different from the shedding caused by A23187 or thrombin. Platelets treated with the PKA inhibitor, H89, presented significant decrease in ristocetin induced platelet aggregation and platelet adhesion on VWF under shear stress. In conclusion, these data provide new evidence that inhibition of PKA results in calpain mediated GPIbα shedding which may play a role in limiting thrombus infinite formation after platelet activation.

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