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PubMed1994

The role of cyclic AMP in the control of sugar transport across the brush-border and basolateral membranes of rat jejunal enterocytes.

Although the involvement of the adenylate cyclase system with glucose transport in the small intestine is poorly understood, there is increasing evidence that cyclic AMP stimulates sugar uptake. In order to study further the effects of cyclic AMP on this process, we have measured glucose accumulation by brush-border and basolateral membrane vesicles prepared from villus enterocytes following exposure of these cells to cyclic AMP and theophylline. Brush-border vesicles derived from enterocytes incubated with cyclic AMP and theophylline accumulated significantly more glucose over a wide range of sugar concentrations, suggesting a change in maximum velocity of the transport system. Glucose uptake by basolateral vesicles was increased at low, but not at high sugar concentrations. Incubation of isolated enterocytes with pancreatic glucagon at concentrations known to stimulate sugar transport by these cells significantly increased enterocyte levels of cyclic AMP. Treatment with glucagon or cyclic AMP resulted in significant hyperpolarization of the potential difference across the brush-border membrane, an important driving force for Na(+)-sugar cotransport. The response to glucagon and cyclic AMP appears to be caused by a decrease in Na+ permeability of the mucosal membrane. Taken together, these results suggest that cyclic AMP is a mediator of the actions of glucagon on enterocytes and provide further evidence for a role of cyclic AMP in the modulation of sugar transport across the intestinal enterocyte.

Animals↗
PubMed1994

Isoproterenol exerts cyclic AMP independent effects on DNA synthesis in cultured adventitial fibroblasts from spontaneously hypertensive and Wistar-Kyoto rats.

Understanding the mechanism behind the growth response evident in the vasculature of the spontaneously hypertensive rat (SHR) remains elusive. Fibroblasts from the aortic adventitial layer of the SHR manifest the heightened proliferative rate in vitro relative to Wistar-Kyoto (WKY) rats that is conspicuous in cultured aortic smooth muscle cells. The adenylylcyclase/cyclic AMP signal transduction pathway is believed to be altered in hypertensive people and animals such that responses to beta-adrenoceptor activation are blunted. The present study examined the effects of beta-adrenoceptor-mediated versus direct activation of adenylylcyclase on intracellular cyclic AMP accumulation and subsequent DNA synthesis in cultured aortic fibroblasts. We hypothesized that elevation of cyclic AMP levels by both isoproterenol and forskolin would normalize the proliferative capacity of SHR fibroblasts. Forskolin increased intracellular cyclic AMP levels and inhibited epidermal growth factor stimulated thymidine incorporation in an equivalent manner in both SHR and WKY adventitial fibroblasts, implying that there is no difference in adenylylcyclase activity. Isoproterenol elevated cyclic AMP levels to a significantly greater degree in the SHR than did forskolin, and yet, relative to forskolin, attenuated growth factor induced DNA synthesis to a lesser extent. These data suggest that isoproterenol, via beta-adrenoceptor activation, exhibits both cyclic AMP dependent and cyclic AMP independent effects in adventitial fibroblasts. The cyclic AMP independent effects of isoproterenol oppose the expected observations due to cyclic AMP and may offer an explanation to the blunted responses to beta-adrenoceptor activation evident both in vitro and in vivo.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Actions of histamine, secretin, and PGE2 on cyclic AMP production by isolated canine fundic mucosal cells.

Cyclic AMP production was studied in isolated canine fundic gastric mucosal cells. Histamine, prostaglandin E2 (PGE2), and secretin increased cyclic AMP production by unenriched mucosal cells. In separated cell fractions, histamine stimulation of cyclic AMP production correlated with the parietal cell content of the fractions. Secretin in concentrations above 1 nM stimulated cyclic AMP production, and this effect correlated with the pepsinogen content of the separated cell fractions. At concentrations above 1 microM, PGE2 stimulated cyclic AMP production; this effect was found in all separated cell fractions and was not associated with any of the available cell markers. PGE2 stimulation of cyclic AMP production was, however, negatively correlated with the parietal cell content. Thus, histamine stimulated cyclic AMP production by parietal cells and secretin stimulated production of cyclic AMP by chief cells. PGE2 stimulation of cyclic AMP production could not be localized to a single cell type but occurred primarily in nonparietal cells.

Animals↗
PubMed1979

Histamine and cyclic AMP in isolated canine parietal cells.

The relationship between cyclic AMP production and the response of isolated canine parietal cells to histamine has been examined. Histamine increased cyclic AMP generation, and this effect correlated with histamine stimulation of oxygen consumption and aminopyrine accumulation. Metiamide inhibited histamine-stimulated cyclic AMP generation and oxygen consumption in a parallel fashion. At concentrations below 100 microM, isobutyl AMP production and oxygen consumption in a similar fashion. However, with IMX above 100 microM, histamine caused no further increases in oxygen consumption, despite markedly enhanced cyclic AMP generation. Neither carbachol nor gastrin increased cyclic AMP production beyond that produced by IMX alone, and the combinations of histamine and carbachol and of histamine and gastrin produced no greater cyclic AMP generation than produced by histamine. These findings support a close relationship between cyclic AMP production and the action of histamine but not of carbachol or gastrin on isolated parietal cells. The mechanisms underlying the potentiating interactions between histamine, carbachol, and gastrin involve step(s) beyond stimulation of cyclic AMP generation.

1-Methyl-3-isobutylxanthine↗
PubMed1975

Coronary artery cyclic AMP content during adrenergic receptor stimulation.

The purpose of this study was to test the hypothesis that the mechanical response of coronary smooth muscle following adrenergic receptor stimulation was mediated by changes in cyclic AMP content. Dibutyryl cyclic AMP caused relaxation of coronary artery strips. Aminophyline caused relaxation and a 254% elevation of cyclic AMP content (P less than 0.005). Phenylephrine caused contraction but no significant change in cyclic AMP content (P greater than 0.4). Epinephrine alone caused contraction and a 99% elevation of cyclic AMP content (P less than 0.001). The alpha blocker, phentolamine, reversed the mechanicaal response to epinephrine, but it did not significantly (P greater than 0.15) reduce the effect of epinephrine on cyclic AMP content. Propranolol enhanced the contractile response to epinephrine and attenuated the epinephrine-induced increase in cyclic AMP content. These results suggest that the contraction of coronary arteries associated with alpha-receptor stimulation is not mediated by changes in cyclic AMP content; however, relaxation associated with beta-receptor stimulation may be mediated by an increase in cyclic AMP content.

Aminophylline↗
PubMed1986

Distribution of cyclic AMP phosphodiesterase in adipose tissue from trained rats.

Fat cells were isolated from sedentary and exercise trained female Sprague-Dawley rats and cyclic AMP phosphodiesterase (cyclic AMP-PDE) activities were determined from crude homogenates of the fat cells in the whole homogenate, P5, P48, and S48 fractions. Exercise training resulted in a significant increase in the mean specific activity of cyclic AMP-PDE (pmol X min-1 X mg-1) from the whole homogenate and S48 fraction at cyclic AMP concentrations of 4, 8, and 16 microM and in the P48 fraction at 8 and 16 microM cyclic AMP. Cyclic AMP-PDE kinetic plots according to Lineweaver-Burk for the calculation of Michaelis constants (Km) and maximum enzyme velocities (Vmax) were nonlinear, indicating both a low and high enzyme form. The Michaelis constants were significantly lower in trained rats than those of its control for the high Km form of cyclic AMP-PDE in the whole and soluble fractions and for the low Km form of the P5 particulate fraction. The Vmax of the high Km form of the P48 particulate fraction from trained animals was also significantly higher than that found in its control. Phosphodiesterase inhibition by methylxanthines in the various fractions was similar in both trained and sedentary animals. These changes in specific activity, Michaelis constants, and Vmax of cyclic AMP-PDE from crude homogenates of isolated fat cells from exercise trained animals may account for the decreased intracellular levels of cyclic AMP following catecholamine stimulation of isolated fat cells from trained rats.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

AMP deaminase binding in rat skeletal muscle after high-intensity running.

Skeletal muscle deaminates a substantial fraction of its adenylate pool to inosine 5'-monophosphate (IMP) when the rate of energy expenditure exceeds supply. How AMP deaminase is activated in vivo is unclear because the substrate affinity is quite low (Michaelis constant approximately 1-2 mM) relative to estimated concentrations of free AMP in skeletal muscle (0.2-1 microM). AMP deaminase:myosin binding causes a large increase in substrate affinity; whether this binding occurs during physiological exercise is uncertain. Exhaustive high-speed (60 m/min) treadmill exercise in rats results in an extensive depletion of adenine nucleotide and a stoichiometric accumulation of IMP (1.5-2 mumol/g) in the superficial vastus lateralis muscles (predominantly fast-twitch white). We measured AMP deaminase:myosin binding after intense exercise and found the bound fraction of AMP deaminase to be increased from 9 +/- 1% at rest to 48 +/- 4% at approximately 45 s after exercise. The extent of binding lessened during recovery from exercise, falling to 32 +/- 4% after approximately 75 s and 21 +/- 2% after approximately 105 s. This postexercise dissociation of AMP deaminase from myosin appeared to be a first-order process (approximately 50 s half time). Treadmill running that leads to deamination also results in AMP deaminase:myosin binding. Binding should activate AMP deaminase and thus favor IMP formation at low physiological concentrations of AMP.

AMP Deaminase↗
PubMed1979

Urinary adenosine 3',5'-monophosphate (cyclic AMP) in normal and cryptorchid boys.

The 24-hour urinary excretion of cyclic AMP was determined in 102 normal boys aged 1.9-16.9 years and in 136 cryptorchids aged 2.5-16.9 years. A marked increase of the normal cyclic AMP excretion was found in pubertal years. There was a positive correlation between urinary excretion of cyclic AMP and the excretion of testosterone, androstenedione, LH and FSH. A positive correlation was also found between cyclic AMP excretion and height and weight, respectively. Mean cyclic AMP excretion of bilateral and unilateral cryptorchids was normal in all bone age groups except in unilateral cases with bone age 8-9.9 years and bone aged greater than or equal to 14 years. In these two groups, mean cyclic AMP excretion was moderately increased. After HCG stimulation of 25 cryptorchids, urinary cyclic AMP excretion varied between increased, unchanged and decreased values. The cyclic AMP excretion changes observed in some of our patients were difficult to interpret and were possibly of unspecific nature. Further information about the testiclar cyclic AMP secretion and the relationship between this nucleotide and sexual hormones may be obtained from studies in testicular biopsy tissue.

Adolescent↗
PubMed1988

Muscarinic cholinergic inhibition of cyclic AMP accumulation in airway smooth muscle. Role of a pertussis toxin-sensitive protein.

Muscarinic agonists are potent constrictors of airway smooth muscle. In many tissues, muscarinic agonists also reduce intracellular cyclic AMP by inhibiting its synthesis. In airway smooth muscle, the role muscarinic agonists have in the regulation of cyclic AMP content is not established. The hypothesis of our study was that muscarinic agonists reduce cyclic AMP accumulation in dog tracheal smooth muscle, and that this reduction involves a pertussis toxin-sensitive regulatory protein (Gi) that couples occupancy of the muscarinic receptor by the agonist to inhibition of adenylate cyclase. We measured cyclic AMP accumulation in tracheal smooth muscle from 4 dogs, and found that acetylcholine (10(-4) M) diminished basal and isoproterenol-stimulated cyclic AMP accumulation by 37.6 +/- 12.1% and 39.4 +/- 1.9%, respectively (mean +/- SEM, p less than 0.05). This reduction of cyclic AMP was dose-dependent and inhibited by atropine (10(-5) M). Incubation of dog tracheal smooth muscle with pertussis toxin (12.5 micrograms/ml) for 21 h catalyzed covalent modification of a membrane protein with an approximate Mr of 40,000. In control strips, acetylcholine decreased isoproterenol-stimulated cyclic AMP content by 33.7 +/- 5.6% (p less than 0.05). However, in strips treated with pertussis toxin (10 micrograms/ml), acetylcholine decreased cyclic AMP by only 7.9 +/- 4.8%; this change was not significant. Thus, pertussis toxin (10 micrograms/ml) attenuated muscarinic cholinergic regulation of cyclic AMP. These findings are consistent with muscarinic cholinergic regulation of adenylate cyclase via Gi in dog tracheal smooth muscle. In addition, the techniques we employed should permit the evaluation of other functions of pertussis toxin-sensitive G proteins in airway smooth muscle.

Acetylcholine↗
PubMed1973

Histamine release induced by human leukocyte lysates. Reabsorption of previously released histamine after exposure to cyclic amp-active agents.

The role of cyclic AMP in histamine release induced by human leukocyte lysates was investigated. Leukocytes were incubated with leukocyte lysates prepared by ultrasonic disruption, and histamine was determined fluorimetrically. Several cyclic AMP-active agents had a marked inhibitory effect on histamine release. Theophylline and isoproterenol produced 50% inhibition at concentrations of less than 10(-5) M. Prostaglandin E(1) and dibutyryl cyclic AMP inhibited release by 50% at 7 x 10(-8) M and 6 x 10(-5) M concentrations, respectively. Histamine, which has recently been shown to increase leukocyte cyclic AMP, had a pronounced inhibitory effect on lysate-induced histamine release, producing 50% inhibition at a concentration of only 2.5 x 10(-12) M.Leukocytes, incubated with leukocyte lysates, were sampled at various times and assayed for free histamine released into the incubation mixture supernates, and for bound histamine associated with the leukocyte buttons after centrifugation. Theophylline, prostaglandin E(1) and dibutyryl cyclic AMP not only blocked histamine release, but also caused a progressive decrease in free histamine when added at any time up to 30 min after initiation of the release reaction. As the free histamine decreased after addition of the inhibitors, there was a corresponding increase in the bound histamine, suggesting that previously released histamine was reabsorbed by the leukocytes after exposure to cyclic AMP-active agents. Continued incubation of leukocytes in their own histamine after completion of the release reaction also resulted in reabsorption of the previously released histamine. Previous studies have indicated that cyclic AMP inhibits leukocyte histamine release. The results of the present studies suggest that cyclic AMP modulates histamine release induced by human leukocyte lysates by stimulating reabsorption of histamine from the extracellular environment. These studies also suggest that previously released extracellular histamine may stimulate its own reabsorption by increasing the intracellular level of cyclic AMP.

Absorption↗
PubMed1973

Alkaline phosphatase. Possible induction by cyclic AMP after cholera enterotoxin administration.

The present studies were undertaken to determine the role, if any, of cyclic 3',5'-adenosine monophosphate (cyclic AMP) as a chemical inducer of rat liver alkaline phosphatase. Cholera enterotoxin, given intravenously to rats, led to a rapid rise in the activity of hepatic adenyl cyclase that was 7(1/2) times greater than control values in 6 h. Cyclic AMP levels were also significantly increased above control values while the activity of cyclic nucleotide phosphodiesterase was unchanged. Hepatic alkaline phosphatase activity was increased 5(1/2) times above control in 12 h, but its rise followed that of adenyl cyclase and cyclic AMP by several hours. Cycloheximide inhibited the rise of hepatic alkaline phosphatase but not that of adenyl cyclase. The administration of glucagon, a known stimulator of hepatic adenyl cyclase, and of dibutyryl cyclic AMP, led to similar striking increases in hepatic alkaline phosphatase activity. This alkaline phosphatase increase was blocked by the prior administration of cycloheximide. Bile duct ligation, a known stimulator of hepatic alkaline phosphatase activity, failed to produce any significant changes in adenyl cyclase or cyclic AMP. Concomitant treatment of rats with bile duct ligation and cholera enterotoxin or bile duct ligation and glucagon, had no additive effect on the increase in hepatic alkaline phosphatase activity, although the increase occurred earlier. These results suggest that: (a) cyclic AMP may act as an inducer of hepatic alkaline phosphatase: (b) the stimulation of hepatic alkaline phosphatase by cholera enterotoxin is mediated by cyclic AMP; (c) the rise in hepatic alkaline phosphatase following bile duct ligation is not mediated by cyclic AMP; (d) the same alkaline phosphatase in rat liver may be induced by two (or more) mechanisms, only one of which requires cyclic AMP.

Adenylyl Cyclases↗
PubMed1982

Cyclic AMP-dependent protein kinase activity and endogenous protein phosphorylation in isolated cortical segments of rabbit nephron.

Cyclic AMP-dependent protein kinase activity and endogenous protein phosphorylating activity are reported for 6 cortical segments of the rabbit nephron which were microdissected and collected according to their morphology. The 6 cortical nephron segments, namely the glomerulus (Glm), proximal convoluted tubule (PCT), proximal straight tubule (PST), cortical ascending limb of Henle's loop (CAL), distal convoluted tubule (DCT), and cortical collecting tubule (CCT), showed protein kinase activities which were increased 1.8-4.9 fold by 10(-6) M cyclic AMP in the presence of histone IIA, histone f2b or histone f3 as a protein substrate. However, all these segments showed little or no cyclic AMP dependent increase of activity with either protamine or alpha-casein as a protein substrate. Cyclic AMP increased the endogenous protein phosphorylation of Glm (10(-6) M cyclic AMP), of CAL (10(-7) and 10(-8) M cyclic AMP), of DCT (10(-6) M cyclic AMP) and of CCT (10(-8), 10(-7) and 10(-6) M cyclic AMP). In contrast, PCT showed decreased endogenous protein phosphorylation in the presence of 10(-7), 10(-5) and 10(-4) M cyclic AMP.

Animals↗
PubMed1975

[A study on the determination method of cyclic AMP in urine by competitive protein binding assay (author's transl)].

The determination method of c-AMP in urine by competitive protein binding assay using the Boehringer Mannheim Laboratory kit was investigated and the results obtained were as follows. 1) Since the angle of the inclination of the standard curve was large, the present method could be used for the determination of c-AMP in concentrations of from 0 to 20p moles. 2) The optimal condition of the binding reaction was for 100 minutes of reaction time at pH 4.0 and 4 degrees C. 3) The specificities of binding protein to the other nucleotides were 0 to adenosine, 0.4 to AMP, 0.3 to ADP, 0.4 to ATP and 0.6 to c-GMP respectively when the specificity to c-AMP was chosen as 100. 4) The optimal volume of cold phosphate buffer solution needed for washing to separate binding c-AMP by filtration method using a millipore filter was 5 approximately 15 ml. 5) The precision of the present method by double determination was 0 arrroximately +/- 11.1% with average of +/-5.6% in c.v. 6) The recovery rate of the added c-AMP by the present method was 78.6 approximately 105.6% with average of 90.1%. 7) Correlation between the determination values of c-AMP of the same samples with the present method and radioimmunosasay (Schwarzman Laboratory Kit) was satisfactorily high with 0.890 in coefficient of correlation, and the determination values by the present method were significantly higher (p less than 0.05) than those by radioimmunoassay. 8) C-AMP in urine was stable for at least one month when the urine was kept frozen. It is conclusively considered from the above results that this competitive protein binding assay is a method to determine c-AMP in urine with excellent accuracy and sensitivity and that this method is useful for clinical test.

Binding, Competitive↗
PubMed1980

[Cyclic-AMP dependent protein kinase activity in the soluble thyrotropin receptor complex (author's transl)].

The relationship between the thyrotropin (TSH) receptor and adenosine 3':5'-monophosphate (cyclic-AMP) dependent protein kinase activity in bovine thyroid plasma membrane fraction was investigated. After solubilization of thyroid plasma membranes, the molecular sizes of TSH binding protein and protein kinase activities were compared using the sucrose density gradient technique. Cyclic-AMP dependent protein kinase activity was present in a soluble thyrotropin receptor fraction. The Km of this enzyme was 2.2 x 10(-6) M for casein substrate in the absence or presence of 10(-5) M cyclic-AMP. A [3H]-cyclic-AMP binding protein was also found in this fraction. The Ka for cyclic-AMP binding was 0.11 x 10(6) M-1, with 3 nmoles per mg protein of total binding capacity. After fractionation using a continuous sucrose density gradient, one of the several [125I]-bovine TSH binding peaks corresponded to a [3H]-cyclic-AMP binding peak. After fractionation on a sucrose density gradient containing 0.4 M NaCl at pH 6.5, a major peak of protein kinase activity was stimulated by adding 10(-5) M cyclic-AMP. A peak of [3H]-cyclic-AMP binding activity corresponded to the same peak. Protein kinase activity in the receptor fraction was stimulated by adding 6 mg/ml bovine TSH. The soluble TSH receptor fraction also had an adenylate cyclase activity stimulated by TSH. These results suggest that some TSH receptors in thyroid plasma membranes have associated adenylate cyclase activity and cyclic-AMP dependent protein kinase activity. The receptor, cyclase, and kinase activities may exist in a functional primary receptor unit which is a component of thyroid plasma membranes.

Adenylyl Cyclases↗
PubMed1979

Comparison of the stimulatory effects of ovine, porcine and human follicle-stimulating hormone and of ovine and human luteinizing hormone on the accumulation of cyclic AMP by porcine granulosa cells.

The effects of ovine, porcine and human FSH, and ovine and human LH on the accumulation of cyclic AMP by porcine granulosa cells obtained from follicles at various stages of maturation were investigated. During incubation periods of 15 min, 10 micrograms ovine FSH pretreated with antiserum to LH or 10 micrograms human FSH resulted in an 11- to 18-fold, five- to ninefold, and less than a twofold increase in intracellular accumulation of cyclic AMP by granulosa cells from small (1--2 mm), medium (3--5 mm) and large (6--12 mm) follicles respectively. Similar patterns of response occurred with addition of porcine FSH. After incubation for 30 and 60 min with ovine, porcine or human FSH, significant accumulation of cyclic AMP in the incubation medium occurred with cells obtained from small and medium-sized follicles. After 60 min of incubation with FSH the accumulation of cyclic AMP in the incubation medium exceeded the intracellular cyclic AMP levels in granulosa cells from small and medium-sized follicles. During incubation periods of 15 min, 1.0 micrograms ovine LH resulted in less than a twofold, a fourfold and greater than a tenfold increase in intracellular accumulation of cyclic AMP by granulosa cells from small, medium and large follicles respectively. Addition of human LH brought about a similar response. Incubation periods of 30 and 60 min with 1.0 micrograms ovine or human LH resulted in significant accumulation of cyclic AMP in the incubation medium by granulosa cells from large follicles; cyclic AMP content in the incubation medium was greater after 60 min compared with 30 min of incubation. It was concluded that ovine FSH pretreated with an antiserum to LH had similar effects on cyclic AMP levels as did purified human and porcine FSH, and that the stimulatory effects of the less pure ovine FSH were probably not due to an impurity in the FSH preparation. Porcine granulosa cells obtained from small follicles should be suitable as an in-vitro FSH bioassay while granulosa cells obtained from large follicles should be suitable as an in-vitro LH bioassay.

Animals↗
PubMed1985

Regulation of cyclic AMP accumulation in lymphoid cells.

We have examined several features of the regulation of cyclic AMP accumulation in lymphoid cells isolated from peripheral blood of human subjects and in the murine T-lymphoma cell line, S49, S49 cells are unique because of the availability of variant clones with lesions in the pathway of cyclic AMP generation and response. We found that human lymphoid cells prepared at 4 degrees C showed substantially greater cyclic AMP accumulation in response to histamine and the beta-adrenergic agonist isoproterenol than did cells prepared at ambient temperature. The muscarinic cholinergic agonist carbamylcholine and peptide hormone somatostatin failed to inhibit cyclic AMP accumulation in human lymphoid cells and treatment with pertussis toxin (which blocks function of Gi, the guanine nucleotide binding protein that mediates inhibition of adenylate cyclase) only minimally increased cyclic AMP levels in these cells. Thus the Gi component of adenylate cyclase appears to play only a small role in modulating cyclic AMP levels in this mixed population of lymphoid cells. Incubation of whole blood with isoproterenol desensitized human lymphocytes to subsequent stimulation with beta agonist. This desensitization was associated with a redistribution of beta-adrenergic receptors such that a substantial portion of the receptors in intact cells could no longer bind a hydrophilic antagonist. Wild-type S49 lymphoma cells showed a similar redistribution of beta-adrenergic receptors after a few minutes' incubation with agonist. Based on studies in S49 variants, this redistribution is independent of components distal to receptors in the adenylate cyclase/cyclic AMP pathway. By contrast, a more slowly developing, agonist-mediated down-regulation of beta-adrenergic receptors was blunted in variants with defective interaction between receptors and Gs, the guanine nucleotide binding protein that mediates stimulation of adenylate cyclase. Unlike results in human lymphoid cells, S49 cells show a prominent inhibition of cyclic AMP accumulation mediated by Gi; this inhibition is promoted by somatostatin and blocked by pertussis toxin. Inhibition by Gi is unable to account for the marked decrease in ability of the diterpene forskolin to maximally stimulate adenylate cyclase in S49 variants having defective Gs. These results emphasize that both Gs and Gi component are important in modulating cyclic AMP accumulation and receptors linked to adenylate cyclase in S49 lymphoma cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗
PubMed1989

[Functional roles of cyclic AMP and cyclic GMP on rabbit urinary bladder and urethral smooth muscle contraction].

It is suggested that cyclic AMP and cyclic GMP play regulatory roles in smooth muscle function. In order to clarify the role of cyclic AMP and cyclic GMP in the function of the lower urinary tract, I examined the effects of isoproterenol and sodium nitroprusside on contractile force and tissue content of cyclic AMP and cyclic GMP. Isoproterenol (10(-8)-10(-4) M) caused a relaxing effect in the rabbit urinary bladder dome, the bladder base and the urethra. The relaxation response by isoproterenol was mediated by cyclic AMP. The relaxation response and the increase in the cyclic AMP level were marked in the bladder dome. Sodium nitroprusside (10(-8)-10(-4) M) also caused a relaxing effect in the rabbit urinary bladder dome, the bladder base and the urethra. The relaxation response to sodium nitroprusside was mediated by cyclic GMP. The relaxation response and the increase in the cyclic GMP level were marked in the urethra. The external addition of derivatives of cyclic AMP and cyclic GMP (dibutyryl cyclic AMP and 8-bromo cyclic GMP, 10(-8)-10(-3) M) also caused a relaxing effect in the bladder dome, the bladder base and the urethra. These results demonstrated that both cyclic AMP and cyclic GMP were related to relaxation of the rabbit lower urinary tract smooth muscle. It seems that cyclic AMP may be mainly related to relaxation of the bladder dome and cyclic GMP may be mainly related to relaxation of the urethra.

Animals↗
PubMed1992

Relationship between cyclic AMP production and lipolysis induced by forskolin in rat fat cells.

Forskolin (7 beta-acetoxy-8, 13-epoxy-1 alpha,6 beta,9 alpha-trihydroxy-labd-14-ene-11-one) induced both cyclic AMP production and lipolysis in intact fat cells, but stimulated lipolysis without increasing cyclic AMP at a concentration of 10(-5) M. Homogenization of fat cells elicited lipolysis without elevation of cyclic AMP. Forskolin did not stimulate lipolysis in the homogenate. Forskolin stimulated both cyclic AMP production and lipolysis in a cell-free system consisting of endogenous lipid droplets and a lipoprotein lipase-free lipase fraction prepared from fat cells. However, at a concentration of 10(-6) M, it induced lipolysis without increase in the cyclic AMP content in this cell-free system. In the cell-free system, homogenization of the lipid droplets resulted in marked increase in lipolysis to almost the same level as that with 10(-4) M forskolin without concomitant increase in cyclic AMP. Addition of forskolin to a cell-free system consisting of homogenized lipid droplets and lipase did not stimulate lipolysis further. Phosphodiesterase activities were found to be almost the same both in the presence and absence of forskolin in these reaction mixtures. Although 10(-3) M forskolin produced maximal concentrations of cyclic AMP: 6.7 x 10(-7) M in fat cells and 2.7 x 10(-7) M in the cell-free system, 10(-4) M cyclic AMP did not stimulate lipolysis in the cell-free system. In a cell-free system consisting of lipid droplets and the lipase, pyrophosphate inhibited forskolin-induced cyclic AMP production, but decreased forskolin-mediated lipolysis only slightly. Based on these results, mechanism of lipolytic action of forskolin was discussed.

Adipose Tissue↗