Tissue Cyclic GMP Content Research Articles

Increased concentrations of cyclic GMP in fetal liver cells stimulated by erythropoietin.

AbstractThe hormone erythropoietin stimulates the processes of cellular proliferation and differentiation in erythroid cells. A possible role for cyclic AMP and cyclic GMP in these events was evaluated in cultures of erythroid cells obtained from the livers of 14-day rat feti. A partially purified preparation of erythropoietin (Ep) stimulated 59Fe incorporation into heme in a dose- and time-dependent manner, indicating that the fetal liver cells were responsive to this hormone. Ep stimulated an increase in tissue cyclic GMP content in these cultures at 4 to 9 hr of incubation. However, exogenous addition of cyclic GMP to cultures did not affect heme synthesis. In correlation studies in which cyclic GMP levels were determined and thymidine incorporation into DNA was monitored, cyclic GMP did not appear to be related to the Ep-induced stimulation of DNA synthesis. Addition of 8-bromo-cyclic GMP to cultures did not increase DNA synthesis and addition of FUdR to cultures did not alter the Ep-induced increase ...

Dissociation between the electrophysiological properties and total tissue cyclic guanosine monophosphate content of guinea pig atria.

The purpose of this study was to investigate the role of cyclic guanosine monophosphate (cyclic GMP) in mediating the direct electrophysiological effects of acetylcholine in guinea pig atria. Acetylcholine significantly diminished spontaneous rate of right atria without increasing cyclic GMP content. Reductions in rate following acetylcholine were augmented by pretreatment with physostigmine, but cyclic GMP levels remained unchanged. In left atria, acetylcholine significantly shortened action potential duration within 5 seconds (both with and without physostigmine pretreatment), but cyclic GMP content was not significantly elevated. Cyclic GMP levels in right atria were significantly increased in response to acetylcholine when the Ca2+ content of the buffer was elevated from 1.25 mM TO 2.5 MM; however, reductions in automaticity in the right atria were not augmented in the high Ca2+ buffer. Marked increases in cyclic GMP content were produced by Na nitroprusside superfusion without changing automaticity of right atria or action potential duration of left atria. Finally, both right and left atria were superfused with cyclic GMP analogs (8-bromo cyclic GMP and dibutyryl cyclic GMP) at high concentrations (10(-4)) for 15 minutes without producing significant effects on spontaneous rate or action potential duration. These results failed to show a correlation between total tissue cyclic GMP content and the electrophysiological effects of acetylcholine on guinea pig atria. The reasons for this are either that cyclic GMP does not mediate directly the electrophysiological effects of acetylcholine, or that small changes in cyclic GMP concentrations, undetectable when total tissue nucleotide levels are measured, occur in discrete effector pools of the cardiac cell to mediate the intracellular effects of the choline ester.

EFFECT OF LUTEINIZING HORMONE ON THE CONCENTRATION OF CYCLIC GMP IN RABBIT OVARIES

Laboratoire d'Endocrinologie, Hôpital Notre-Dame et Département de Medicine, Université de Montréal, Montréal, Canada (Received 28 June 1978) Cyclic AMP has been implicated as an intermediate in some of the actions of luteinizing hormone (LH) on ovarian tissues, such as stimulation of steroidogenesis (LeMaire & Marsh, 1975). Both in vitro (Marsh, Butcher, Savard & Sutherland, 1966) and in vivo (Armstrong, Dorrington & Robinson, 1976), stimulation with LH results in a rapid increase in the amount of cyclic AMP in ovarian tissues, which precedes the LH-induced increase in steroidogenesis. Recently, studies on rat ovaries (Grinwich, Ham, Hichens & Behrman, 1976; Ratner, 1976; Ratner & Sanborn, 1976) have indicated that the ovarian tissue content of cyclic GMP may also be regulated by LH, but in a direction opposite to that of cyclic AMP. In the rabbit, Goff & Major (1975) have shown that administration of human chorionic gonadotrophin (HCG) causes a biphasic increase

Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in rat ductus deferens

SMOOTH muscle tone seems to be primarily regulated by the concentration of free calcium in cytoplasm1,2. Several agents that cause smooth muscle contraction increase the tissue content of cyclic GMP with no significant change or only small reduction of the cyclic AMP concentration3–7. It has been suggested5–7 that cyclic GMP may be casually involved in the contractile response of smooth muscle and that this nucleotide may act as a comediator with calcium to promote contraction. Several observations, however, are not consistent with this assumption. Although increases both in tissue tonus1,2 and in the cyclic GMP level8–10 induced by hormones and neurotransmitters are generally dependent on the presence of extracellular calcium and seem to be secondary to increased influx of calcium into the cytoplasm, the correlation between these two calcium-dependent events is poor in various tissues10–16. On the basis of such observations, we have suggested that cyclic GMP may act as a negative feedback inhibitor of hormonally stimulated calcium influx into cytoplasm8,10,11. We have studied the effects of various agents on cyclic nucleotide levels in the ductus deferens of the rat, and report here that many smooth muscle relaxants, including sodium nitroprusside (SNP), increase cyclic GMP levels in the ductus deferens.

Effects of insulin on diaphragm muscle independent of the variation of tissue levels of cyclic AMP and cyclic GMP

The hypothesis that effects of insulin are mediated by an increase in cyclic GMP was examined in “intact” and “cut” hemidiaphragm preparations. After preincubation for 30 min, the diaphragms were exposed to insulin (10 mU/ml) for periods of time varying from 2 to 10 min. Then the tissue content of cyclic GMP was measured by radioimmunoassay. Tissue cyclic GMP levels were not altered by the addition of insulin, although the incorporation of d-[U- 14C]glucose into glycogen was strongly stimulated under the same conditions. When cyclic GMP and dibutyryl cyclic GMP in concentrations covering a wide range were added to the medium, the insulin-like effect on glycogen synthesis could not be reproduced. On the other hand, the high concentration of dibutyryl cyclic AMP in the medium failed to suppress the insulin effect on transmembrane transport of l-arabinose under conditions in which the entrance of this nucleotide into a cell was confirmed by a significant reduction in glycogenesis. Our results suggest that the effects of insulin on striated muscle may be unrelated to either cyclic GMP or cyclic AMP.

Role of muscarinic cholinergic receptors in regulation of guanosine 3':5'-cyclic monophosphate content in mammalian brain, heart muscle, and intestinal smooth muscle.

Effects of acetylcholine and of agents that mimic or block its physiological actions have been studied upon concentrations of guanosine 3':5'-cyclic monophosphate (cyclic GMP) and adenosine 3':5'-cyclic monophosphate (cyclic AMP) in slices of mammalian cerebral cortex, heart ventricle, and ileum. Acetylcholine, and cholinomimetic agents with a predominantly muscarinic action, such as methacholine, bethanechol, and pilocarpine, induced an increase in the concentration of cyclic GMP, accompanied by no change or a slight decrease in the concentration of cyclic AMP, in all three tissues studied. Tetramethylammonium, a cholinomimetic agent with a predominantly nicotinic action, on the other hand, did not significantly alter concentrations of either cyclic GMP or cyclic AMP. The increase in the tissue content of cyclic GMP induced by acetylcholine and its muscarinic analogs was antagonized by atropine, a muscarinic blocking agent, but not by hexamethonium, a nicotinic blocking agent. These and other results suggest the generalization that the interaction of acetylcholine with muscarinic receptors, but not with nicotinic receptors, causes an increase in the concentration of cyclic GMP. The data are compatible with the hypothesis that cyclic GMP may mediate the muscarinic actions of acetylcholine. The antagonistic actions of cholinergic and adrenergic agents on the physiology of contraction of intestinal smooth muscle and of cardiac muscle are reflected in, and may result from, antagonistic actions of these compounds on the levels of both cyclic GMP and cyclic AMP in these tissues.