Cyclic nucleotides, calcium, bicarbonate, and protein secretion in canine pancreatic juice in response to cholecystokinin–pancreozymin

1979 ◽  
Vol 57 (6) ◽  
pp. 541-546 ◽  
Author(s):  
H. L. Cailla ◽  
H. Sarles ◽  
M. V. Singer
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Juice ◽  
Cyclic Gmp ◽  
Cyclic Nucleotides ◽  
Parallel Increase ◽  
Calcium Bicarbonate ◽  
Strong Linear Correlation ◽  
Protein Output ◽  
Dose Dependent ◽  
Stimulation Of

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin–pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg−1 h−1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg−1 h−1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg−1 h−1 of CCK and later for 12 and 24 U kg−1 h−1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.

scholarly journals The influence of intracellular levels of cyclic nucleotides on cell proliferation and the induction of antibody synthesis.

1975 ◽  
Vol 141 (1) ◽  
pp. 97-111 ◽  
Author(s):  
J Watson
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Cyclic Nucleotides ◽  
Precursor Cells ◽  
Cyclic Monophosphate ◽  
The Absolute ◽  
Stimulation Of ◽  
Mitogenic Signal

The intracellular ratio of adenosine 3',5'-cyclic monophosphate (cyclic AMP) to guanosine 3',5'-cyclic monophosphate (cyclic GMP) may control the developmental pathway followed by antibody-forming cell (AFC) precursors. The evidence for this is derived from several different types of experiments. First lipopolysaccharide (LPS) which is mitogenic for B lymphocytes, stimulates rapid, transient changes in intracellular levels of cyclic GMP but not cyclic AMP when added to mouse spleen cultures. Cyclic GMP itself stimulates DNA synthesis in these cultures, suggesting that the intracellular changes in cyclic GMP levels are involved in the mitogenic signal delivered by LPS to cells. The absolute amounts of cyclic nucleotides may vary widely in different cells under various conditions, however, the intracellular ratio of cyclic AMP to cyclic GMP is always high in nondividing cells and low in dividing cells. AFC precursors appear to respond to antigen in the absence of T-cell activity by inactivation (1-7). In the response to antigen in the presence of specific T cells, precursor cells proliferate and mature to AFC. Raising intracellular levels of cyclic AMP inhibits cell proliferation and leads to precursor cell inactivation (14, 15). It is suggested that the interaction of antigen with immunoglobulin receptors on the surface of precursors cells leads to the stimulation of adenylate cyclase activity and initiates the inactivation pathway. Since cyclic GMP stimulates immune responses in T-cell-depleted cultures (14, 15) and increasing cyclic GMP levels appear to be involved in the delivery of a mitogenic signal to cells, it is suggested that T-helper cells deliver a signal to precursor cells via the stimulation of guanylate cyclase to initiate the inductive pathway. It is suggested that it is the intracellular ratio of cyclic AMP to cyclic GMP that regulates the fate of precursor cells, not the absolute level of one cyclic nucleotide.

Regulation of oxytocin secretion by the ovine corpus luteum: effect of activators of protein kinase C

1990 ◽  
Vol 124 (2) ◽  
pp. 225-232 ◽  
Author(s):  
J. J. Hirst ◽  
G. E. Rice ◽  
G. Jenkin ◽  
G. D. Thorburn
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Corpus Luteum ◽  
Phospholipase C ◽  
Tissue Slices ◽  
Kinase C ◽  
Luteal Tissue ◽  
Dose Dependent ◽  
Stimulation Of

ABSTRACT The effect of protein kinase C activation and dibutyryl cyclic AMP on oxytocin secretion by ovine luteal tissue slices was investigated. Several putative regulators of luteal oxytocin secretion were also examined. Oxytocin was secreted by luteal tissue slices at a basal rate of 234·4 ± 32·8 pmol/g per h (n = 24) during 60-min incubations.Activators of protein kinase C: phorbol 12,13-dibutyrate (n = 8), phorbol 12-myristate,13-acetate (n = 4) and 1,2-didecanoylglycerol (n = 5), caused a dose-dependent stimulation of oxytocin secretion in the presence of a calcium ionophore (A23187; 0·2 μmol/l). Phospholipase C (PLC; 50–250 units/l) also caused a dose-dependent stimulation of oxytocin secretion by luteal slices. Phospholipase C-stimulated oxytocin secretion was potentiated by the addition of an inhibitor of diacylglycerol kinase (R59 022; n = 4). These data suggest that the activation of protein kinase C has a role in the stimulation of luteal oxytocin secretion. The results are also consistent with the involvement of protein kinase C in PLC-stimulated oxytocin secretion. The cyclic AMP second messenger system does not appear to be involved in the control of oxytocin secretion by the corpus luteum. Journal of Endocrinology (1990) 124, 225–232

Mutant analysis suggests that cyclic GMP mediates the cyclic AMP-induced Ca2+ uptake in Dictyostelium

1991 ◽  
Vol 99 (1) ◽  
pp. 187-191
Author(s):  
S. Menz ◽  
J. Bumann ◽  
E. Jaworski ◽  
D. Malchow
Keyword(s):  
Cyclic Amp ◽  
Mutant Strain ◽  
Cyclic Gmp ◽  
Parental Strain ◽  
Dependent Manner ◽  
Heavy Chains ◽  
Signal Relay ◽  
Sensitive Electrode ◽  
Dose Dependent ◽  
Cyclic Amp Synthesis

Previous work has shown that streamer F (stmF) mutants of Dictyostelium discoideum exhibit prolonged chemotactic elongation in aggregation fields. The mutants carry an altered structural gene for cyclic GMP phosphodiesterase resulting in low activities of this enzyme. Chemotactic stimulation by cyclic AMP causes a rapid transient increase in the cyclic GMP concentration followed by association of myosin heavy chains with the cytoskeleton. Both events persist several times longer in stmF mutants than in the parental strain, indicating that the change in association of myosin with the cytoskeleton is transmitted directly or indirectly by cyclic GMP. We measured the cyclic AMP-induced Ca2+ uptake with a Ca(2+)-sensitive electrode and found that Ca2+ uptake was prolonged in stmF mutants but not in the parental strain. The G alpha 2 mutant strain HC33 (fgdA), devoid of InsP3 release and receptor/guanylate cyclase coupling, lacked Ca2+ uptake. However, the latter response and cyclic GMP formation were normal in the signal-relay mutant strain agip 53 where cyclic AMP-stimulated cyclic AMP synthesis is absent. LiCl, which inhibits InsP3 formation in Dictyostelium, blocked Ca2+ uptake in a dose-dependent manner. The data indicate that the receptor-mediated Ca2+ uptake depends on the InsP3 pathway and is regulated by cyclic GMP. The rate of Ca2+ uptake was correlated in time with the association of myosin with the cytoskeleton, suggesting that Ca2+ uptake is involved in the motility response of the cells.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

1979 ◽  
Vol 237 (5) ◽  
pp. C200-C204 ◽  
Author(s):  
D. J. Stewart ◽  
J. Sax ◽  
R. Funk ◽  
A. K. Sen
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Salt Gland ◽  
Domestic Ducks ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

Effect of histamine on canine gastric mucosal adenylate cyclase.

1977 ◽  
Vol 232 (1) ◽  
pp. E35
Author(s):  
R R Dozois ◽  
A Wollin ◽  
R D Rettmann ◽  
T P Dousa
Keyword(s):  
Gastric Mucosa ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Antral Mucosa ◽  
Fundic Mucosa ◽  
H2 Receptors ◽  
Dose Dependent ◽  
Stimulation Of

The effects of histamine, Nalpha-dimethylhistamine, 4,5-methylhistamine, Ntau-methylhistamine, pentagastrin, carbachol, and NaF on the adenylate cyclase activity from canine gastric mucosa were investigated in cell-free preparations. In gastric fundic mucosa, histamine (10(-4) M), Nalpha-dimethylhistamine (10(-4) M), 4,5-methylhistamine (10(-4 M), and NaF (10)-2) M) significantly (P less than 0.001) increased adenylate cyclase activity (means+/-SE) by 44.7+/-6.6, 49.4+/-6.7, 34.0+/-6.4, and 572.0+/-100%, respectively, above basal activity. The effect of histamine and Na-dimethyl histamine was dose-dependent. In contrast, other tested agents failed to stimulate the formation of cyclic AMP in gastric fundic mucosa. Metiamide (10(-4) M) blocked the stimulation of fundic mucosa adenylate cyclase by histamine and Nalpha-dimethylhistamine, without significantly altering basal and NaF-induced adenylate cyclase activity. Histamine, however, did not stimulate the adenylate cyclase activity from the gastric antral mucosa. The findings support the proposal that the canine gastric acid response to histamine may be mediated by cyclic AMP formed in response to stimulation of histamine H2-receptors.

scholarly journals The Role of Cyclic Nucleotides in the CNS

1977 ◽  
Vol 4 (3) ◽  
pp. 151-195 ◽  
Author(s):  
John W. Phillis
Keyword(s):  
Cyclic Amp ◽  
Synaptic Transmission ◽  
Cyclic Gmp ◽  
Adenosine Receptor ◽  
Cyclic Nucleotides ◽  
Phosphodiesterase Inhibitors ◽  
Adenosine Uptake ◽  
Injection Techniques ◽  
Firm Basis

SUMMARY:On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre- or postsynaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intracellular injection techniques should minimize this particular problem, although possibly at the expense of new difficulties. Prior blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Ultimately, the development of highly specific inhibitors for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the actions of cyclic GMP and the role of its synthesizing enzyme, guanylale cyclase.The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature.

scholarly journals THE MODULATING INFLUENCE OF CYCLIC NUCLEOTIDES UPON LYMPHOCYTE-MEDIATED CYTOTOXICITY

1973 ◽  
Vol 138 (2) ◽  
pp. 381-393 ◽  
Author(s):  
Terry B. Strom ◽  
Charles B. Carpenter ◽  
Marvin R. Garovoy ◽  
K. Frank Austen ◽  
John P. Merrill ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Cyclic Gmp ◽  
Cyclic Nucleotides ◽  
Prostaglandin E1 ◽  
Cell Interaction ◽  
Target Cells ◽  
Cholinergic Stimulation ◽  
Initial Cell ◽  
Initial Interaction

The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor alloantigens is modulated by the cellular levels of cyclic AMP and cyclic GMP. Increases in the cyclic AMP levels of attacking lymphocytes by stimulation with prostaglandin E1, isoproterenol, and cholera toxin inhibit lymphocyte-mediated cytotoxicity; whereas, depletion of cyclic AMP with imidazole enhances cytotoxicity. The augmentation of cytotoxicity produced by cholinergic stimulation with carbamylcholine is not associated with alterations in cyclic AMP levels and is duplicated by 8-bromo-cyclic GMP. The effects of activators of adenylate cyclase, cholinomimetic agents, and 8-bromocyclic GMP are upon the attacking and not the target cells and occur at the time of initial interaction of attacking and target cells. Indeed, the level of cyclic nucleotide (cyclic AMP and cyclic GMP) at the time of initial cell-to-cell interaction determines the extent of cytotoxicity.

scholarly journals Growth hormone, cyclic nucleotides and the rapid control of translation in heart muscle

1975 ◽  
Vol 152 (3) ◽  
pp. 583-592 ◽  
Author(s):  
J Mowbray ◽  
J A Davies ◽  
D J Bates ◽  
C J Jones
Keyword(s):  
Growth Hormone ◽  
Protein Synthesis ◽  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Cyclic Nucleotides ◽  
Cyclic Nucleotide ◽  
Precursor Pool ◽  
Growth Hormone Action ◽  
Constant Rate ◽  
The Individual

Perfused rat heart incorporated L-[14C]tyrosine into protein at a constant rate for up to 75 min. A purified bovine growth-hormone preparation (1 mug/ml) stimulated the incorporation to a new constant rate that was more than three times the control rate by 10 min after hormone addition to perfusate. The hormone, however, did not alter the intracellular tracer amino acid pool, and the relationship of this to the aminoacyl-tRNA precursor pool is discussed. It is concluded that the increased incorporation largely reflected a rapid increase in protein synthesis at the ribosomes. Measurements of cyclic nucleotide contents during the perfusion showed that these appeared to vary in a systematic way during the perfusion. This strands in contrast with the constant values given by several other parameters measured in this preparation. Futher, the cyclic nucleotide variation seems to be independent of external effectors. The steady-state performance of the heart correlates more closely the [cyclic AMP]/[cyclic GMP] ratio than with the content of the individual cyclic nucleotides. At 10 min after the addition of growth hormone a slight decrese in cyclic AMP content and a large decrease in cyclic GMP were found, suggesting that the hormone's effect in stimulating protein synthesis may be mediated by a decrease in cyclic nucleotide concentrations or an increase in the [cyclic AMP]/[cyclic |p] ratio. The findings are also consistent with an intracellularly directed role for these nucleotides, and the possibility that the cyclic nucleotide changes are an indirect result of growth-hormone action is discussed.

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