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PubMed1975

Regulation of cyclic AMP content in normal and malignant brain cells.

Pharmacologic characterization of the neurotransmitter-sensitive cyclic AMP-second messenger systems of brain has proven to be a complex and difficult endeavor. At least two types of receptor appear to be involved in the mediation of the effects of NE on cyclic AMP content. One of these receptor systems appears to mediate the potentiation by NE of the effect of adenosine of cyclic AMP accumulation. The cellular heterogeneity of brain has retarded the determination of the mechanism underlying the synergistic interaction of catecholamines and adenosine. An attempt to use clonal cell lines to examine the action of NE and adenosine on cyclic AMP content has resulted in the demonstration that adenosine acts in a hormone-like fashion to stimulate adenylate cyclase activity. However, the studies did not shed light on the mechanism of synergism. An increasing number of reports are appearing which support the idea that the responsiveness of cells to neuronally released NE may involve adaptive changes in the responsiveness of the cyclic AMP-second messenger system which compensate for chronic over- or underproduction of the first messenger, NE. Evidence was presented that such a regulatory process may be operative in rat cerebral cortex. Our studies of catecholamine-induced loss of responsiveness in human astrocytoma cells have led us to the conclusion that the loss in the capacity of the cells to accumulate cyclic AMP is a result of a loss in the capacity to synthesize cyclic AMP. However, it is probable that different cells make use of different mechanisms (e.g., changes in phosphodiesterase activity) to regulate their ability to respond to hormones or neurotransmitters. The physiologic importance of this level of regulation of responsiveness to hormones is not known at this time.

Adenosine↗
PubMed1975

Modulation of stimulated acid secretion by dibutyryl cyclic AMP in the dog stomach.

An in vivo canine gastric chamber preparation was used to determine effects of exogenous cyclic AMP and dibutyryl cyclic AMP on histamine-driven acid secretion and the role of blood flow in these responses. Histamine was infused intravenously at a submaximal rate 1.2 mu/kg-min) followed by the intraarterial infusion of either cyclic AMP (0.15 mg/kg-min) or dibutyryl cyclic AMP (0.15 mg/kg-min. Acid secretion and mucosal blood flow (aminopyrine clearance) were measured at 15-minute intervals, and electrical potential difference was measured continuously. Histamine alone decreased the potential difference from 82 mV to 48 mV within 60 minutes, increased aminopyrine clearance from 1.0 ml/min to 2.4 ml/min and increased acid output to 220 muEq/15 min. All values returned towards control following termination of histamine infusion. Dibutyryl cyclic AMP significantly increased histamine stimulated acid secretion to 350 muEq/15 min, but did not alter mucosal blood flow or electrical potential. Cyclic AMP did not change secretory, circulatory or electrical response to histamine. Therefore, dibutyryl cyclic AMP appears to increase histamine-stimulated acid secretion, and the effect is not mediated by increased mucosal blood flow.

Aminopyrine↗
PubMed1975

Lack of feedback regulation of cyclic 3':5'-AMP accumulation by free fatty acids in chicken fat cells.

Fat cells isolated from the mesenteric adipose tissue of chickens (pullets) responded to glucagon with an increase in lipolysis and a sustained rise in cyclic adenosine 3':5'-monophosphate (cyclic AMP) over a 30-min incubation. The prolonged accumulation of cyclic AMP due to glucagon in chicken fat cells was primarily intracellular. In addition, there was little increase in cyclic AMP accumulation due to theophylline alone or potentiation of the increase due to glucagon. These data indicate that chicken fat cells, unlike rat fat cells, are relatively insensitive to theophylline. Neither lipolysis nor cyclic AMP accumulation by chicken fat cells was inhibited by free fatty acid to albumin ratios (3 to 7) which markedly reduced both events in rat fat cells. However, in the absence of albumin from the medium, lipolysis in chicken fat cells was reduced, but not to the same extent as in rat fat cells. Chicken fat cells did accumulate more intracellular free fatty acids in response to lipolytic agents than did rat fat cells. The uptake of oleate by rat and chicken fat cells was identical. Glucagon-induced accumulation of cyclic AMP by chicken fat cell ghosts was unaffected by added oleate. Under identical conditions glucagon-induced adenylate cyclase activity of rat fat cell ghosts was markedly inhibited by added oleate. Triglyceride lipase activity of the pH 5.2 precipitate from a 40,000 x g infranatant of homogenized fat cells from chickens was less sensitive than that from rat fat cells to the ratio of oleate to albumin. These results suggest that the maintenance of cyclic AMP levels in chicken fat cells incubated with lipolytic agents results from the relative insensitivity of chicken fat cells to free fatty acid inhibition of cyclic AMP accumulation.

Adenosine Deaminase↗
PubMed1976

Cyclic AMP in pancreatic acinar cells: effects of gastrointestinal hormones.

In the presence of 5 mM theophylline, secretin and vasoactive intestinal peptide (VIP) each increased cyclic adenosine 3':5'-monophosphate (cyclic AMP) in acinar cells isolated from guinea pig pancreas. Without theophylline, neither peptide altered cellular cyclic AMP. Glucagon, which is similar to secretin and VIP both in chemical structure and spectrum of biologic activities, neither stimulated cellular cyclic AMP nor inhibited the stimulation produced by secretin or by VIP. Other agents which were tested and found not to increase cellular cyclic AMP were cholecystokinin, carboxyl-terminal octapeptide of cholecystokinin, gastrin I, gastrin II, bovine pancreatic polypeptide, carbamylcholine, and prostaglandin E1. Neither carboxyl-terminal octapeptide nor gastrin I altered the stimulation of cellular cyclic AMP produced by secretin or VIP. With natural secretin a significant increase in cellular cyclic AMP could be detected at concentrations as low as 3 x 10(-10) M and maximal stimulation occurred at 10(-8) M. VIP was approximately 1% as potent as natural secretin and maximal concentrations of secretin plus VIP increased cellular cyclic AMP to the same value as was obtained with a maximal concentration of secretin alone.

Animals↗
PubMed1976

Regulation of antibody response in vitro. X. Biphasic effect of cyclic AMP on the secondary anti-hapten antibody response to anti-immunoglobulin and enhancing soluble factor.

The effect of elevation of an intracellular cyclic AMP level on in vitro anti-hapten antibody response was studied, by using mesenteric lymph node cells of rabbits which were primed with dinitrophenylated Ascaris antigen (DNP-Asc) or DNP-ragweed antigen (DNP-Rag). The anti-hapten antibody response was induced by stimulation of the primed B cells by either DNP-heterologous carrier conjugate or anti-immunoglobulin (anti-Ig) for 24 hr (first stage), followed by 6-day culture of the activated cells in the presence of nonspecific enhancing factor (second stage). The stimulation with anti-Ig induced IgG anti-hapten antibody response and enhanced the formation of total IgG. Addition of dibutyryl cyclic AMP or aminophylline with anti-Ig or DNP-heterologous carrier during the first stage enhanced IgG anti-hapten antibody response. The optimal concentration of these reagents for the enhancement was 5 x 10(-4) M to 10(-3) M. The presence of 5 x 10(-6) M prostaglandin E1 during the first stage also enhanced the antibody response. Similarly, the presence of dibutyryl cyclic AMP or aminophylline during the stimulation of DNP-Rag-primed cells with homologous antigen (first stage) enhanced the antibody response. If the same concentration of dibutyryl cyclic AMP or aminophylline was added together with enhancing soluble factor during the second stage after the stimulation of the primed cells with anti-Ig, both the antibody response and the formation of IgG were suppressed. The antibody response of DNP-Rag-primed cells stimulated with homologous antigen was also suppressed if dibutyryl cyclic AMP or aminophylline was added during the subsequent culture (second stage). Evidence was obtained that suppression of antibody response by cyclic AMP during the second stage is probably due to inhibition of the proliferation of B cells. Neither of these drugs suppressed the formation of enhancing soluble factor from the carrier-specific cells stimulated with the homologous carrier. The results obtained in the present experiments suggested that stimulation of hapten-primed B cells with anti-gamma chain in the presence of an optimal concentration of dibutyryl cyclic AMP resulted in the formation of a significant amount of IgG anti-DNP antibody without participation of T cells.

Animals↗
PubMed1976

Androgenic effects on protein kinases and cyclic AMP-binding protein in the ventral prostate.

Androgenic deprivation resulted in marked impairment of prostate weight and significant alterations in cytosolic and particulate protein kinase activities and cyclic AMP-binding capacity of this tissue. Whereas rats orchidectomized for 7 days exhibited significant enhancement in the specific activity of cytosolic cyclic AMP-dependent (73%) and -independent (45%) protein kinases as well as cyclic AMP-binding protein (196%), administration of testosterone (5.0 mg/100 g, i.m., 5 days) exerted little or no effect in reversing these responses. In contrast, when expressed as total enzyme activity per prostate, castration led to marked decreases in protein kinase activity assayed in the presence (87%) and absence of the cyclic nucleotide (91%). Likewise, the cyclic AMP-binding capacity of the soluble enzyme was depressed (77%) following androgenic deprivation. Although testosterone treatment for 3 days significantly reversed these effects, complete restoration was not achieved even after 5 days of androgen replacement therapy. Moreover, while exogenous cyclic AMP had no effect on protein kinase activity from crude nuclear preparations, the phosphorylation of endogenous nuclear substrates was dependent on androgenic status of the animals. Whereas castration produced decreases in the specific and total activity of prostatic particulate protein kinase as well as the cyclic AMP-binding protein, testosterone replenishment was effective in abolishing these alterations seen in orchidectomized rats. Data from the present study provide additional support to the concept that changes in cyclic AMP-adenylate cyclase-protein kinase system play an important role in the overall mechanism(s) by which male sex steroids exert their diverse anabolic effects on male accessory sex tissues.

Androgens↗
PubMed1976

Activation of cyclic AMP phosphodiesterase by a new vitamin E derivative.

The effects of sodium alpha-tocopherol phosphate (TPNa), a new vitamin E derivative, on cyclic nucleotide phosphodiesterases from a soluble supernatant fraction of rat liver were investigated. TPNa produced a dose-dependent increase in cyclic AMP hydrolysis at a low substrate concentration (1 muM cyclic AMP), whereas the compound inhibited the hydrolytic activity at a high substrate level (100 muM cyclic AMP). Cyclic GMP phosphodiesterase activity was suppressed by TPNa regardless of the substrate concentration. The addition of TPNa did not change the apparent Km value (50 muM) of cyclic AMP phosphodiesterase at low substrate level (less than 5 muM). In contrast, at higher substrate concentration, the concave downward curve observed in a Lineweaver-Burk plot became straight in the presence of TPNa. Low concentrations of cyclic GMP, which are known to activate cyclic AMP hydrolysis, showed an additive effect on cyclic AMP phosphodiesterase only when a submaximal concentration of cyclic GMP was present in addition to TPNa. These and other data suggest that TPNa modifies cyclic AMP phosphodiesterase in all allosteric fashion.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Motor disturbances produced by intrastriatal injection of cyclic AMP and cyclic GMP.

Male albino rats were permanently cannulated bilaterally in the caudate/putamen nucleus and subsequently injected unilaterally with cyclic AMP or cyclic GMP. Both of these cyclic nucleotides failed to produce any obvious change in motor activity. The concomitant intrastriatal injection of carbachol and cyclic AMP resulted in enhancement of the carbachol-induced dyskinesias. Under similar conditions, cyclic GMP blocked the carbachol effects. The dibutyryl (db) derivatives of cyclic AMP and cyclic GMP both enhanced the carbachol-induced dyskinesias and both db cyclic nucleotides induced dyskinesias when injected intrastriatally alone. The concomitant intrastriatal injection of dopamine and carbachol resulted in a blockade of the carbachol-induced dyskinesias. Dopmaine had no effect on db cyclic AMP and db cyclic GMP dyskinesias. The db cyclic AMP effects characteristically involved the distal limb musculature, while the db cycle GMP effects largely involved the proximal limb and trunk muscles. The hypothesis for opposing action of cyclic AMP and cyclic GMP in the CNS and the discrepancy between the effects of intrastriatal injection of cyclic AMP and dopamine were discussed.

Animals↗
PubMed1977

Modulation of Fc-mediated phagocytosis by cyclic AMP and insulin in a macrophage-like cell line.

Studies on genetically selected mutants in phagocytosis of E[IgG] indicated that the defect in some mutants could be corrected by addition of 8 Br-cAMP, and suggested that cyclic AMP may be involved in the mechanism of phagocytosis through the Fc receptor. In order to elucidate the role of cyclic AMP in phagocytosis in the parental, nonmutant macrophage-like cell line, J774.2, it was necessary to employ restrictive conditions which rendered phagocytosis suboptimal. When 4774.2 cells were cultured in nontissue culture Petri dishes phagocytosis was markedly reduced. Addition of 8 Br-cAMP or inducers of intracellular cyclic AMP such as isoproterenol restored the phagocytic ability of these cells. Similarly, treatment of the parental J774.2 cells with insulin reduced the level of phagocytosis, and once again this suppression could be corrected by addition of 8 Br-cAMP. In no case did AMP mimic the effects of 8 Br-cAMP. The effect of cyclic AMP action in this system was not instantaneous, but rather reached optimal levels at 5 to 10 hr, suggesting that cyclic AMP is not the immediate signal for phagocytosis. The genetic analysis of macrophage variants may provide a useful model for studies on the mechanisms of phagocytosis, and also the effects of insulin and cyclic AMP on an easily measurable biologic function in a specialized cell type.

Cell Line↗
PubMed1979

Studies on cyclic nucleotides in the adrenal gland. IX. Effects of ACTH on cyclic AMP and steroid production by the zona fasciculata-reticularis of the adrenal cortex.

Effects of ACTH and calcium on cyclic AMP and steroid production by the zona fasciculata-reticularis (the decapsulated fraction) from the rat adrenal cortex have been studied. Increasing concentrations of extracellular calcium enhanced the action of ACTH on cyclic AMP and steroid production. These effects of ACTH with calcium were prevented by lanthanum, but not by tetracaine or verapamil, suggesting that ACTH stimulation may be mediated by calcium through a process not involving the tetracaine- or verapamil-vulnerable step(s) of the calcium current. High concentrations of external calcium itself increased cyclic AMP accumulation without any increase in steroidogenesis. A calcium ionophore, X537A was stimulatory for steroidogenesis but inhibitory with respect to cyclic AMP accumulation. Considered together with the findings of AMP increase, these results suggest that ACTH primarily increases intracellular calcium mobilization thus stimulating directly the steroidogenesis, which is independent of the cyclic AMP system. Relatively high concentrations of ACTH activate the adenylate cyclase, which depends on extracellular calcium to increase cyclic AMP levels and stimulation of steroidogenesis by the decapsulated fractions of the adrenal cortex.

Adrenal Cortex↗
PubMed1979

Effects of coronary vasodilator on cyclic nucleotides. The concentrations of cyclic AMP and cyclic GMP in canine coronary artery and left ventricular muscle following the administration of various coronary vasodilators.

We examined the effects of various coronary vasodilator drugs, papaverine, dipyridamole, isosorbide dinitrate, amyl nitrite, nitroglycerin, diltiazem, and nifedipine, on cyclic nucleotides of the coronary artery and left ventricular muscle of anesthetized dogs at maximum coronary blood flow after the administration of each agents. Only papaverine and dipyridamole significantly increased the concentration of c-AMP in the coronary artery. Nitroglycerin and siosorbide dinitrate did not significantly change the concentration of c-AMP but rather increased the concentration of c-GMP. Coronary vasodilator drugs were divided into three groups in association with the relationship of cyclic nucleotides in the coronary artery. Group I, including papaverine, dipyridamole, and amyl nitrite, increased the concentration of c-AMP and the ratio of c-AMP to c-GMP. Group II, including nitroglycerin and isosorbide dinitrate, incrased the concentration of c-GMP and decreased the ratio of c-AMP to c-GMP. Group III, including nifedipine and diltiazem, had no effect on the cyclic nucleotides. Group I drugs also increased the concentration of c-AMP in the left ventricular muscle and so group I drugs may predispose the ischemic heart to develop ventricular arrhythmias. It seems that the most useful coronary vasodilator is no effect on the c-AMP in the ventricular muscle and group II and group III drugs are more useful coronary vasodilator drugs than group I drugs.

Amyl Nitrite↗
PubMed1989

Calcium-dependent effects of maitotoxin on phosphoinositide breakdown and on cyclic AMP accumulation in PC12 and NCB-20 cells.

The marine dinoflagellate toxin maitotoxin (MTX) stimulates phosphoinositide breakdown in pheochromocytoma PC12 cells and in neuroblastoma hybrid NCB-20 cells. In both cell lines, the stimulation of phosphoinositide breakdown by MTX is dependent on extracellular calcium, but it is not reduced by organic or inorganic calcium channel blockers. In PC12 cells, the maximal stimulation of phosphoinositide breakdown occurs at 1.5 mM [Ca2+]o, whereas in NCB-20 cells the maximal stimulation is observed at 2.5-4.5 mM [Ca2+]o. Phosphoinositide breakdown is known to lead to formation of both inositol phosphates and diacylglycerols. The latter, through stimulation of protein kinase C, would, like phorbol esters, be expected to augment cyclic AMP accumulation in PC12 cells and to inhibit receptor-mediated cyclic AMP accumulation in NCB-20 cells. MTX does potentiate forskolin-induced accumulation of cyclic AMP in PC12 cells and does inhibit prostaglandin E2-induced accumulation of cyclic AMP in NCB-20 cells. The effects of MTX on accumulation of cyclic AMP are calcium dependent and the concentrations of calcium required for maximal responses are the same as the ones required for maximal stimulation of phosphoinositide breakdown. MTX increases intracellular calcium in both cell lines, as measured by calcium-quin2 fluorescence. But the effects of MTX on forskolin- and prostaglandin E2-mediated cyclic AMP accumulation are not mimicked by a calcium ionophore and are not blocked by nifedipine, a calcium channel blocker. Translocation of protein kinase C occurs after treatment with MTX in both cell lines; the protein kinase C activity and content are reduced in the cytosol and increased in membranes after exposure to either MTX or a phorbol ester. The results confirm previous studies on the heterogeneous input of protein kinase C to cyclic AMP-generating systems performed with phorbol esters and demonstrate the utility of MTX as a unique tool for studies of systems that involve second messengers generated through stimulation of phosphoinositide breakdown.

Adrenal Gland Neoplasms↗
PubMed1989

[Study of the effect of sclareol glycol diterpene on the 3',5'-AMP level].

Sclareol glycol (SG) is a semisynthetic diterpene of the labdanic group. SG is tetranorlabdaniol bivalent alcohol 13, 14, 15, 16-tetranorlabdan-8 alpha, 12-diol, obtained from the plant Salvia sclarea L., grown in Bulgaria. The effects of SG were studied on the level of 3',5'-AMP in:mono-layer tissue cultures of the anterior hypophysis of the rat; in hypophysial and brain tissue during in vitro incubation; in liver microsomes of the rat during in vitro incubation and in liver perfusate of the rat. It was established that SG induced an increase in accumulation of 3,5'-AMP in the tissues from the anterior hypophyses of mature and newborn rats, in the sections of brain cortex and cerebellum of mature rats. Similar changes were found by the diterpene forskolin, studied comparatively. SG induced a reduction of accumulation of 3',5'-AMP in liver microsomes and diminished the release of 3',5'-AMP in a liver perfusate of the rat. The increased accumulation of 3',5'-AMP due to SG could be explained by postreceptor stimulation of the enzyme adenylate cyclase, binding directly to its catalytic subunit. The reduced accumulation of 3',5'-AMP in liver microsomes and its diminished release in liver perfusate could be explained either by activation of the inhibitory adenylate cyclase in hepatocytes or by desensitisation of 3',5'-AMP-generating system.

Animals↗
PubMed1988

Cyclic AMP-dependent protein kinase activity in Trypanosoma cruzi.

A cyclic AMP-dependent protein kinase activity from epimastigote forms of Trypanosoma cruzi was characterized. Cytosolic extracts were chromatographed on DEAE-cellulose columns, giving two peaks of kinase activity, which were eluted at 0.15 M- and 0.32 M-NaCl respectively. The second activity peak was stimulated by nanomolar concentrations of cyclic AMP. In addition, a cyclic AMP-binding protein co-eluted with the second kinase activity peak. Cyclic AMP-dependent protein kinase activity was further purified by gel filtration, affinity chromatography on histone-agarose and cyclic AMP-agarose, as well as by chromatography on CM-Sephadex. The enzyme ('holoenzyme') could be partially dissociated into two different components: 'catalytic' and 'regulatory'. The 'regulatory' component had specific binding for cyclic AMP, and it inhibited phosphotransferase activity of the homologous 'catalytic component' or of the 'catalytic subunit' from bovine heart. Cyclic AMP reversed these inhibitions. A 'holoenzyme preparation' was phosphorylated in the absence of exogenous phosphate acceptor and analysed by polyacrylamide-gel electrophoresis. A 56 kDa band was phosphorylated. The same preparation was analysed by Western blotting, by using polyclonal antibodies to the regulatory subunits of protein kinases type I or II. Both antibodies reacted with the 56 kDa band.

Animals↗
PubMed1985

Pertussis toxin treatment blocks the inhibition of somatostatin and increases the stimulation by forskolin of cyclic AMP accumulation and adrenocorticotropin secretion from mouse anterior pituitary tumor cells.

Somatostatin (SRIF) inhibits stimulated cyclic AMP accumulation and adrenocorticotropin (ACTH) release from mouse anterior pituitary tumor cells (AtT-20/D16-16). In order to determine whether guanine nucleotide inhibitory proteins (Ni) mediate these effects, AtT-20 cells were treated with pertussis toxin, an agent that inactivates Ni. Pertussis toxin catalyses the ADP-ribosylation of a 41,000 MW protein in membranes of AtT-20 cells. Pretreatment with pertussis toxin prevents the subsequent ability of toxin to catalyse the labeling of Ni. This effect is dependent on the time of pretreatment and is not reversible. The inhibition of SRIF of forskolin-stimulated cyclic AMP accumulation and ACTH release is prevented by pertussis toxin treatment. The blockade is dependent on the time and concentration of toxin used and is not reversible. Pertussis toxin treatment prevents SRIF from inhibiting corticotropin releasing factor and cholera toxin-stimulated cyclic AMP synthesis. The inhibition of K+ and 8-bromocyclic AMP-stimulated ACTH release by SRIF is attenuated partially by toxin treatment. The ability of forskolin and cholera toxin to stimulate cyclic AMP formation and ACTH release is enhanced by treatment of AtT-20 cells with pertussis toxin. The increased cyclic AMP response to forskolin is prevented by cycloheximide. The data indicate that Ni mediates the inhibition by SRIF of cyclic AMP formation and the ACTH release that results from adenylate cyclase stimulation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Cyclic AMP potentiates the retinoic acid-induced expression of tissue transglutaminase in peritoneal macrophages.

Fresh serum and retinoids induce the expression of tissue transglutaminase in cultured mouse resident peritoneal macrophages. Analogues of cyclic AMP, such as dibutyryl cyclic AMP, and agents that increase intracellular cyclic AMP levels enhance the induction. Dibutyryl cyclic AMP alone has little effect on transglutaminase expression, but it increases the sensitivity of macrophages to low concentrations of either serum or retinoic acid. Dibutyryl cyclic AMP potentiates the transglutaminase-inducing activity of both free retinoic acid and retinoic acid bound to the serum retinol-binding protein. Pretreating macrophages with dibutyryl cyclic AMP or retinoic acid does not prime the cells to respond to the other agent; instead, both agents must be present simultaneously to obtain the synergistic induction of transglutaminase. Our studies suggest that the modulation of intracellular cyclic AMP levels may have pronounced effects on retinoic acid-induced gene expression in myeloid cells.

Animals↗
PubMed1984

Acute elevation of cyclic AMP does not alter the ion-conducting properties of the neuronal nicotinic acetylcholine receptor of PC12 cells.

The nicotinic acetylcholine receptor of Torpedo californica has been shown to be subject to cyclic AMP-dependent phosphorylation, raising the possibility that nicotinic receptors may be regulatable by phosphorylation. To investigate this possibility for a neuronal nicotinic receptor, we have studied the effects of elevation of cyclic AMP on the ion-conducting properties of the nicotinic receptor of PC12 cells. The cyclic AMP content of the cells was altered by exposure to various concentrations of forskolin (an activator of adenylate cyclase) for periods of time ranging from 1 to 40 min. Receptor activation then was measured as agonist-induced influx of 86Rb+ into the cells. Throughout a variety of conditions, no changes in agonist-induced ion influx were detected. This was true regardless of the concentration of agonist used, the duration of receptor stimulation that was measured, the concentration of forskolin employed, or the duration of elevation of cyclic AMP prior to receptor activation. Experiments designed to measure receptor desensitization also were unable to detect any differences upon elevation of cyclic AMP. Finally, the antagonism of receptor activation by substance P also was not affected by elevation of cyclic AMP. Thus, no evidence could be obtained in these cells supporting the hypothesis that a neuronal nicotinic acetylcholine receptor can be acutely regulated by changes in cellular cyclic AMP.

Adenylyl Cyclases↗
PubMed1980

Role of cyclic AMP in insulin release evoked by glucose and other secretagogues.

A close coupling in time-course and dose-dependency exists between cyclic AMP and insulin responses to glucose as tested in isolated islets of Langerhans from the rate and other species. Other secretagogues are also capable of inducing a cyclic AMP response. Under circumstances where the insulin response is reduced, secretion can, however, proceed without a measurable increase in cyclic AMP. "Classical" cyclic AMP-raising agents such as the methylxanthines are unable to induce substantial insulin release in the absence of glucose; however, short-term previous exposure to 27.7 mM glucose transforms 3-isobutyl-1-methylxanthine into a potent insulin-releasing agent. It is concluded that 1) all secretagogues share the stimulation of cyclic AMP as part of the insulinogenic signal; 2) a cyclic AMP response may be needed only for optimal secretory responsiveness of the B-cell; 3) whether a rise in cyclic AMP is solely sufficient to trigger insulin secretion depends on the extent to which a "memory" of exposure to glucose is present in the B-cell.

1-Methyl-3-isobutylxanthine↗