Correlation of cyclic AMP and cyclic GMP levels with changes in contractile force of dog ventricular myocardium during cholinergic antagonism of positive inotropic actions of histamine, glucagon, theophylline and papaverine.

1. Rat hearts were perfused with 32Pi, and contractile force was increased by positive inotropic agents (agents that increase contractility). The inhibitory subunit of troponin (troponin I) was then isolated by affinity chromatography in 8M-urea, and its 32P content measured. Incorporation of phosphate into the subunit was calculated on the basis of the [gamma-32P]ATP specific radioactivity in the hearts. 2. When hearts were perfused with 30 nM-DL-isoprenaline (N-isopropylnoradrenaline), there was an increase in contractile force over 30s which was paralleled by an increase in troponin I phosphorylation. When hearts were perfused for 25s with increasing concentrations of isoprenaline from 1 NM to 0.6 muM, there was again a parallel increase in contractile force and troponin I phosphorylation. The maximum phosphorylation observed was 1.5 mol of phosphate/mol of troponin I, which was reached after 25s with 0.1 muM-isoprenaline. 3. Hearts were stimulated with a 15s pulse perfusion of 30nM-DL-isoprenaline. There was an increase in contractile force which was followed by a return to the control value within 50s. Troponin I phosphorylation increased to a plateau value which was reached within 30s, and remained constant for 60s after the isoprenaline pulse. Phosphorylase a and 3′:5′-cyclic AMP concentration showed changes similar to that of the contractile force. There was no change in 3′:5′-cyclic GMP concentration. 4. When hearts stimulated with a 15S pulse of isoprenaline were subsequently perfused with 0.6 muM-acetylcholine, the changes in contractile force, phosphorylase a and 3′:5′-cyclic AMP were very similar to those seen with the 15s pulse of isoprenaline alone. Troponin I phosphorylation increased to a maximum 30s after the end of the isoprenaline pulse, but then rapidly decreased during the subsequent 30s. This decrease was preceded by a 60% increase in the concentration of 3′:5′-cyclic GMP. 5. Hearts were perfused with 0.2 muM-glucagon for periods up to 60s. Contractile force showed little change for the first 30s, but then increased rapidly. This was paralleled by changes in 3′:5′-cyclic AMP concentration. Troponin I phosphorylation increased slowly, but the increase in contractile force had reached a maximum before significant phosphorylation had occurred. 6. It is concluded that under certain conditions, e.g. immediately after β-adrenergic stimulation, there is a good correlation between contractile force and troponin I phosphorylation. However, under other conditions, e.g. when contractile force is decreasing after removal of β-adrenergic stimulation or in the presence of glucagon, contractile force and troponin I phosphorylation are not well correlated. These results suggest that mechanisms for modifying cardiac contractility, other than troponin I phosphorylation, must be present in rat heart.

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Effect of Cyclic AMP and Cyclic GMP on Thromboplastin (Factor III) Synthesis in Human Monocytes In Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665317 ◽

1983 ◽

Vol 50 (04) ◽

pp. 804-809 ◽

Cited By ~ 16

Author(s):

Torstein Lyberg

Keyword(s):

Cyclic Amp ◽

Cyclic Gmp ◽

Immune Complexes ◽

Phosphodiesterase Inhibitors ◽

Inhibitory Effect ◽

Intracellular Camp ◽

Human Monocytes ◽

Purified Protein Derivative ◽

A 23187

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.

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Cellular localization of cyclic AMP and cyclic GMP in rat bone marrow

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)66975-1 ◽

1979 ◽

Vol 29 ◽

pp. 85

Author(s):

Nobuyoshi Yoshida ◽

Kohtaro Taniyama ◽

Chikako Tanaka

Keyword(s):

Bone Marrow ◽

Cyclic Amp ◽

Cyclic Gmp ◽

Cellular Localization ◽

Rat Bone

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Melanocyte-stimulating hormone and the regulation of tyrosinase activity in hair follicular melanocytes of the mouse

Journal of Endocrinology ◽

10.1677/joe.0.1110225 ◽

1986 ◽

Vol 111 (2) ◽

pp. 225-232 ◽

Cited By ~ 29

Author(s):

S. A. Burchill ◽

A. J. Thody

Keyword(s):

Cyclic Amp ◽

Cyclic Gmp ◽

Hair Growth ◽

Yellow Pigment ◽

Tyrosinase Activity ◽

Melanocyte Stimulating Hormone ◽

Golden Yellow ◽

Skin Explants ◽

Low Levels ◽

Old Mice

ABSTRACT Skin tyrosinase activity increases during hair growth in C3H–HeA*vy mice and reaches higher levels in young (30- to 35-day-old) mice when the hair follicular melanocytes synthesize the black pigment, eumelanin, than in older (6-month-old) mice when they produce the golden yellow pigment, phaeomelanin. To examine the regulation of the melanocytes at these different stages we have compared the effect of α-MSH and other agents that act, through cyclic AMP-dependent mechanisms, on skin tyrosinase activity in both young and old mice during hair growth, initiated by plucking. Daily administration of α-MSH, isoprenaline or theophylline increased coat darkness, and skin tyrosinase activity in the younger mice 7–9 days after plucking, but they were ineffective in the older mice. Similarly α-MSH, 8-bromo-cyclic AMP or theophylline increased tyrosinase activity in skin explants from the younger mice incubated for up to 24 h but had no effect in explants from older mice. Cyclic GMP had no effect on tyrosinase activity in skin explants from both young and old mice. It is suggested that whereas cyclic AMP-dependent mechanisms may operate to regulate tyrosinase activity in the hair follicular melanocytes of younger mice that produce eumelanin these systems may not operate in the older mice when these melanocytes synthesize phaeomelanin. Phaeomelanin synthesis, unlike that of eumelanin, may not depend upon tyrosinase and its regulation by cyclic AMP and this could explain the low levels of this enzyme in the skin and its failure to respond to α-MSH and other activators of the cyclic AMP system during periods of phaeomelanin production. J. Endocr. (1986) 111, 225–232

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