The Effects Of Derivatives Of Adenosine 3',5'-Monophosphate On Fluid Secretion By The Salivary Glands Of Calliphora

1973 ◽  
Vol 59 (3) ◽  
pp. 595-606
Author(s):  
M. J. BERRIDGE

1. The nature of the cyclic AMP-receptor interaction was analysed by testing a range of cyclic nucleotides on the isolated salivary glands of adult blowflies. 2. All compounds containing modifications in the region of ribose or the phosphate ring were inactive. One compound, adenosine 3',5'-phosphorothioate, appeared to compete with cyclic AMP. 3. A number of nucleotides with alterations restricted to the base region of the molecule could stimulate secretion equally as well as cyclic AMP. 4. These observations indicate that during the action of cyclic AMP the phosphate ring and ribose sugar are critical whereas the adenine ring plays a relatively unspecific role.

1970 ◽  
Vol 53 (1) ◽  
pp. 171-186 ◽  
Author(s):  
M. J. BERRIDGE

1. Isolated salivary glands of Calliphora have been used as a system on which to study the mode of action of a hormone. 2. Cyclic AMP, which is thought to mediate the action of many different hormones, can stimulate fluid secretion equally as well as 5-HT. 3. Methyl xanthines, which inhibit the hydrolysis of intracellular cyclic AMP by phosphodiesterase, can stimulate secretion and prolong recovery time after removal of 5-HT. 4. Methyl xanthines can sensitize salivary glands to both 5-HT and cyclic AMP. 5. Butyryl derivatives of cyclic AMP can stimulate secretion, but their effect is slower and lasts longer. 6. Certain amino acids and malate support fluid secretion more effectively than trehalose or glucose. 7. It is concluded that cyclic AMP plays an important role in the ability of 5-HT to control fluid secretion by salivary glands.


1979 ◽  
Vol 78 (1) ◽  
pp. 137-148
Author(s):  
MICHAEL J. BERRIDGE ◽  
HERBERT LIPKE

The efflux of 45Ca from prelabelled salivary glands was studied under a variety of conditions. 5-Hydroxytryptamine (5-HT) or cyclic AMP caused a large release of label most of which entered the saliva. The ionophore A23187 caused a similar release of calcium but EGTA had no effect. The presence of an active calcium pump on the lumenal surface was investigated further by studying calcium transport across the gland. This transport of calcium, which provides a measure of calcium entry into the cell, was very sensitive to 5-HT concentration but little affected by cyclic AMP. The small cyclic AMP-dependent transport was depressed by 8-bromo cyclic GMP with a parallel fall in the rate of fluid secretion. These studies provide more direct evidence that 5-HT acts to stimulate the entry of external calcium in addition to mobilizing internal calcium. Note: On sabbatical leave from the University of Massachusetts, Boston.


1978 ◽  
Vol 39 (02) ◽  
pp. 404-410 ◽  
Author(s):  
F I Pareti ◽  
D Carrera ◽  
L Mannucci ◽  
P M Mannucci

SummaryDerivatives of cyclic nucleotides were evaluated for their ability to inhibit platelet aggregation and the release reaction. Derivatives substituted in position 8 (mainly 8-Br-cyclic GMP) were more active than 3’-5’ cyclic AMP, and their relative potency in inhibiting platelet aggregation and 14C-serotonin release was comparable to that of N62-0’-dibutyryl-cyclic AMP. Compounds substituted in position 6 or 2’-0 were not effective. The active compounds, which were also tested for their ability to stimulate platelet adenylate cyclase or to inhibit cyclic AMP phosphodiesterase, did not modify the intracellular levels of cyclic AMP. Since previous animal experiments have shown that these derivatives cause less side effects than cyclic AMP and its dibutyryl derivative in animals, it is suggested that modification of the cyclophosphate molecule might make it possible to find compounds active only on platelet function without interfering with other biological systems.


Rate of fluid secretion by the salivary glands of the blowfly Calliphora is regulated by 5-hydroxytryptamine (5-HT) working in conjunction with cyclic AMP. Although cyclic AMP can exactly mimic the acceleration of fluid secretion produced by 5-HT, the underlying electrical events are completely different. Transepithelial potentials were measured by a liquid paraffin-gap technique which permits continuous potential recordings during rapid changes of the bathing medium. The potential of the lumen of unstimulated glands is + 5 mV with respect to the bathing medium but becomes — 10 to 20 mV after applying 5-HT. After stimulation with cyclic AMP, however, the luminal potential becomes more positive (+ 30 to 40 mV). A similar effect is obtained with theophylline or when glands are treated with 5-HT in the presence of an impermeant anion such as isethionate. These observations suggest that in addition to stimulating the synthesis of cyclic AMP, 5-HT may also act directly to increase anion movement. Cyclic AMP appears to stimulate cation transport, which explains the increase in positive potential obtained when this compound (or theophylline) is applied in the absence of 5-HT.


1979 ◽  
Vol 27 (5) ◽  
pp. 913-923 ◽  
Author(s):  
E M Rosenberg ◽  
G LaVallee ◽  
P Weber ◽  
S M Tucci

Immunohistochemical studies employing antibodies against cyclic nucleotides indicate that cyclic AMP and cyclic GMP are localized to distinct subcellular sites. These antibodies, however, cross-react weakly with noncyclic nucleotides (eg. ATP, GTP), and therefore we investigated the speficity of the immunohistochemical technique. Slides of fetal nuclei exposed to gaseous nitrous acid demonstrated reduced immunofluorescence. The slides were then incubated with cyclic and noncyclic nucleotides, and restoration of distinct cyclic AMP and cyclic GMP staining pattern was achieved only with appropriate cyclic nucleotides. Antibodies that were used have a greater affinity for acetylated derivatives of cyclic nucleotides. By using a gas phase technique, tissue slices were acetylated and immunohistochemical staining intensity was compared with the effect of acetylation on antibody affinity for various nucleotides. Acetylation greatly increased affinity of cyclic AMP antibody for cyclic AMP but not other nucleotides, and greatly intensified cyclic AMP staining. Acetylation moderately increased affinity of cyclic GMP antibody for cyclic GMP, and moderately intensified cyclic GMP staining. Conclusion: Both nitrous acid and acetylation studies support the specificity of the immunohistochemical method for cyclic nucleotides.


1981 ◽  
Vol 200 (3) ◽  
pp. 509-514 ◽  
Author(s):  
B Bréant ◽  
S Keppens ◽  
H De Wulf

Vasopressin and alpha-adrenergic agonists are known to be potent cyclic AMP-independent Ca2+-dependent activators of liver glycogen phosphorylase. When hepatocytes are pre-incubated with increasing concentrations of vasopressin or of the alpha-agonist phenylephrine, they become progressively unresponsive to a second addition of the respective agonist. The relative abilities of six vasopressin analogues and of five alpha-agonists to activate glycogen phosphorylase and to cause subsequent desensitization are highly correlated, indicating that the same vasopressin and alpha-adrenergic receptors are involved in both responses. About 5-times-higher peptide concentrations are needed to desensitize the cells than to activate their glycogen phosphorylase, whereas the concentrations of alpha-agonists required for the desensitization are only twice those needed for the activation of phosphorylase. The desensitization is not mediated by a perturbation in the agonist-receptor interaction. It is clearly heterologous, i.e. it is not agonist-specific, and must therefore involve a mechanism common to both series of agonists. The evidence for a role of Ca2+ movements or phosphatidylinositol turnover is briefly discussed.


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