Xanthine derivatives without PDE effect stimulate voltage-activated chloride conductance of toad skin

2003 ◽  
Vol 284 (2) ◽  
pp. C521-C527 ◽  
Author(s):  
Wolfram Nagel ◽  
Uri Katz
Keyword(s):  
Intracellular Camp ◽  
Voltage Sensitivity ◽  
Inhibitory Effects ◽  
Amphibian Skin ◽  
Toad Skin ◽  
Camp Content ◽  
Xanthine Derivatives ◽  
X 32 ◽  
Intracellular Camp Content ◽  
Stimulation Of

The effect of xanthine derivatives on the voltage-activated Cl− conductance ( G Cl) of amphibian skin was analyzed. 3-Isobutyl-1-methylxanthine (IBMX) and the recently synthesized xanthine derivatives 3,7-dimethyl-1-propyl xanthine (X-32) and 3,7-dimethyl-1-isobutyl xanthine (X-33), which lack inhibitory effects on phosphodiesterases in CHO and Calu-3 cells, increased voltage-activated G Cl without effect on baseline conductance at inactivating voltage. Half-maximal stimulation of G Cl occurred at 108 ± 9 μM for X-32 and X-33 after apical or basolateral application. The stimulation of G Cl, which occurs only in the presence of Cl− in the mucosal solution, is caused by a shift of the voltage sensitivity to lower clamp potentials and an increase of the maximally activated level. Furosemide reversed both the shift of sensitivity and the increase in magnitude. These patterns are fundamentally different from those seen after application of membrane-permeant, nonmetabolized analogs of cAMP, and they indicate that the xanthines stimulate G Cl directly. This notion is strengthened by the lack of influence on intracellular cAMP content, which is consistent with the observations in CHO and Calu-3 cells. We propose that the xanthine derivatives increase the voltage sensitivity of a regulative component in the conductive Cl− pathway across amphibian skin.

Effects of PGI2 and Its More Stable Forms on the Aggregation and on the Camp Content of Human Platelets

1979 ◽  
Author(s):  
E. Nemesánszky ◽  
I. Blaskó ◽  
I. Stadler ◽  
G. Sas ◽  
L. A. Pálos
Keyword(s):  
Ethyl Ester ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Intracellular Camp ◽  
Camp Content ◽  
Prolonged Duration ◽  
Potent Inhibitory Effect ◽  
Stable Forms ◽  
Derivatives Of ◽  
Intracellular Camp Content

The authors investigated the anti-aggregating properties of some relatively stable derivatives of PGI2 concurrently determining the intracellular cAMP content of platelets. The ethyl-ester derivative of PGI2 and the complexes of PGI2-ethyl ester with β-cyclodextrine proved to be more stable than PGI2-sodium salt. Their stimulating effect on adenyl-cyclase correlated with the potent inhibitory effect on platelet aggregation as well. The enhancing effect of these compounds for the intracellular cAMP content have a prolonged duration time -lasting 300 minutes- compared with the only a few minutes’ effect of PGE1.These stable forms of PGI2 might be clinically useful as highly effective antiaggregating compounds.

Effects of PGI2 and its more Stable forms on the Aggregation and on the Camp Content of Human Platelets

1979 ◽  
Author(s):  
E. Nemesánszky ◽  
Gy. Blaskó ◽  
I. Stadler ◽  
G. Sas ◽  
L.A. Pálos
Keyword(s):  
Ethyl Ester ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Adenyl Cyclase ◽  
Intracellular Camp ◽  
Camp Content ◽  
Potent Inhibitory Effect ◽  
Stable Forms ◽  
Derivatives Of ◽  
Intracellular Camp Content

The authors investigated the anti-aggregating properties of some relatively stable derivatives of PGI2 concurrently determining the intracellular cAMP content of platelets. The ethyl-ester derivative of PGI2 and the complexes of PGI2-ethyl ester with β-cyclodextrine proved to be mora stable than PGI2-sodium salt. Their stimulating effect on adenyl-cyclase correlated with the potent inhibitory effect on platelet aggregation as well. The enhancing effect of these compounds for the intracellular cAMP conten t have a prolonged dura tion time -las ting 300 minutes - compared with the only a few minutes’ effect of PGE1.These stable forms of PGI2 might be clinically useful as highly effective anti-aggregating compounds.

scholarly journals Mechanisms of leptin secretion from white adipocytes

2002 ◽  
Vol 283 (1) ◽  
pp. C244-C250 ◽  
Author(s):  
Philippe G. Cammisotto ◽  
Ludwik J. Bukowiecki
Keyword(s):  
Intracellular Camp ◽  
Adenylate Cyclase System ◽  
Inhibitory Effects ◽  
High Affinity ◽  
White Adipocytes ◽  
Selective Antagonists ◽  
Camp Levels ◽  
Lipolytic Hormones ◽  
Phosphodiesterase Iii ◽  
Stimulation Of

The mechanisms regulating leptin secretion were investigated in isolated rat white adipocytes. Insulin (1–100 nM) linearly stimulated leptin secretion from incubated adipocytes for at least 2 h. The adrenergic agonists norepinephrine, isoproterenol (two nonselective β-agonists), or CL-316243 (potent β3) all inhibited insulin (10 nM)-stimulated leptin release. The inhibitory effects of norepinephrine and isoproterenol could be reversed not only by the nonselective antagonist propranolol but also by the selective antagonists ICI-89406 (β1) or ICI-118551 (β2), the β2-antagonist being less effective than the β1. Insulin-stimulated leptin secretion could also be inhibited by a series of agents increasing intracellular cAMP levels, such as lipolytic hormones (ACTH and thyrotropin-stimulating hormone), various nonhydrolyzable cAMP analogs, pertussis toxin, forskolin, methylxanthines (caffeine, theophylline, IBMX), and specific inhibitors of phosphodiesterase III (imazodan, milrinone, and amrinone). Significantly, antilipolytic agents other than insulin (adenosine, nicotinic acid, acipimox, and orthovanadate) did not mimic the acute stimulatory effects of insulin on leptin secretion under these conditions. We conclude that norepinephrine specifically inhibits insulin-stimulated leptin secretion not only via the low-affinity β3-adrenoceptors but also via the high-affinity β1/β2-adrenoceptors. Moreover, it is suggested that 1) activation of phosphodiesterase III by insulin represents an important metabolic step in stimulation of leptin secretion, and 2) lipolytic hormones competitively counterregulate the stimulatory effects of insulin by activating the adenylate cyclase system.

Effects of calcium antagonist TMB-8 on active Na and Cl transport in rabbit ileum

1986 ◽  
Vol 250 (5) ◽  
pp. G691-G697 ◽  
Author(s):  
M. Donowitz ◽  
S. Cusolito ◽  
G. W. Sharp
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Electrolyte Transport ◽  
Intracellular Camp ◽  
Bathing Solution ◽  
Rabbit Ileum ◽  
Camp Content ◽  
Cl Transport ◽  
Transport Effects ◽  
Intracellular Camp Content

The effects of 3,4,5-trimethoxybenzoate 8-(N,N-diethylamino)octyl ester (TMB-8), an agent that traps calcium within intracellular stores, were studied on active electrolyte transport in rabbit ileum under basal conditions and after altering transport by increasing the intracellular cAMP content or by exposure to two agonists that act by altering intracellular Ca2+ (carbachol and serotonin). TMB-8 decreased the ileal short-circuit current and increased active Na and Cl absorption by increasing the mucosal-to-serosal Na and Cl fluxes. These effects were reversed by increasing the bathing solution Ca2+ to 4 mM, a concentration that itself did not alter basal ileal transport. The maximum glucose- and amino acid (alanine)-induced increase in Na absorption in the ileum was not affected by TMB-8. The effects on basal transport of TMB-8 were not associated with a change in 45Ca2+ entry across the ileal serosal surface. TMB-8 did not alter cAMP-induced secretion, as judged by its lack of effect on the increase in short-circuit current caused by 8-bromo-cAMP (10(-4) M). TMB-8 totally prevented the transport effects of carbachol but did not inhibit the effects of serotonin. These data suggest a role for intracellular Ca2+ in regulation of basal ileal Na and Cl transport but not in cAMP-induced secretion. There appear to be several pools of intracellular Ca2+ involved in neurohumoral effects on active electrolyte transport.

scholarly journals Mechanism of bile salt-induced mucin secretion by cultured dog gallbladder epithelial cells

1996 ◽  
Vol 316 (3) ◽  
pp. 873-877 ◽  
Author(s):  
J. Henriëtte KLINKSPOOR ◽  
Guido N. J. TYTGAT ◽  
Sum P. LEE ◽  
Albert K. GROEN
Keyword(s):  
Epithelial Cells ◽  
Bile Salt ◽  
Bile Salts ◽  
Cholesterol Gallstone ◽  
Direct Interaction ◽  
Gallstone Formation ◽  
Intracellular Camp ◽  
Mucin Secretion ◽  
Camp Content ◽  
Intracellular Camp Content

1. Hypersecretion of gallbladder mucin has been proposed to be a pathogenic factor in cholesterol gallstone formation. Using cultured gallbladder epithelial cells, we demonstrated that bile salts regulate mucin secretion by the gallbladder epithelium. In the present study we have investigated whether established second messenger pathways are involved in bile salt-induced mucin secretion. 2. The effect of activators and inhibitors on mucin secretion was studied by measuring the secretion of [3H]N-acetyl-D-glucosamine-labelled glycoproteins. Intracellular cAMP content of the cells was measured using a radioimmunoassay. 3. Incubation of the cells with 10 mM taurocholate did not increase the intracellular cAMP content (25.7 versus control 22.8 pmol of cAMP/mg of protein). No stimulation of mucin secretion was observed after incubation with 1–100 μM concentrations of the calcium ionophores ionomycin and A23187. The stimulatory effect of 10 mM tauroursodeoxycholate (TUDC) on mucin secretion could not be inhibited by the addition of EDTA. Activation of protein kinase C (PKC) by 1 μg/ml phorbol 12-myristate 13-acetate (PMA) caused an increase in mucin secretion (342% versus control 100%), comparable with the effect of 40 mM TUDC. The effect of 10 ng/ml PMA could partially be inhibited by a concentration of 2 μM of the PKC inhibitor staurosporin. Staurosporin had no inhibitory effect on mucin secretion induced by TUDC. 4. In gallbladder epithelial cells bile salts do not stimulate mucin secretion via one of the classical signal transduction pathways. We hypothesize that bile salts act on mucin secretion via a direct interaction with the apical membrane.

Interaction between amrinone and parathyroid hormone on bone in culture

1982 ◽  
Vol 243 (6) ◽  
pp. E499-E504
Author(s):  
N. S. Krieger ◽  
P. H. Stern
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Direct Interaction ◽  
Inhibitory Effects ◽  
Dihydroxyvitamin D3 ◽  
Basal Bone ◽  
Cardiotonic Agent ◽  
Neonatal Mouse Calvaria ◽  
Dose Dependent ◽  
Stimulation Of

The cardiotonic agent amrinone has been postulated to directly affect Na-Ca exchange. Because stimulated bone resorption has been proposed to require Na-Ca exchange, we examined the effects of amrinone on bone. Amrinone inhibited release of Ca from neonatal mouse calvaria in organ culture stimulated by parathyroid hormone (PTH), 1,25-dihydroxyvitamin d3, or prostaglandin E2. Inhibition was dose dependent and maximal at 2 X 10(-4) M. The effect of amrinone differed from the inhibitory effects of calcitonin, ouabain, or nigericin in that 1) 6-h exposure to amrinone alone prevented the effect of subsequently added PTH; 2) amrinone was only partially effective if added after resorption was initiated by 24-h treatment with PTH; 3) coincubation with amrinone and PTH during the first 48 h of culture allowed for a response to PTH after amrinone was removed; no such protection by a stimulator occurred with ouabain or nigericin. Also submaximal concentrations of amrinone plus calcitonin, ouabain, or nigericin gave greater than additive inhibition of Ca release. Amrinone had no effect on basal bone cAMP or on the acute stimulation of cAMP by PTH. The results suggest that amrinone could have a more direct interaction with the pathway involved in stimulated bone resorption than the other inhibitors.

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