Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present work shows the existence of adenosine-dependent cyclic adenosine monophosphate (AMP) accumulation in the chick optic tectum. When tecta from 18-day-old embryos were incubated with the phosphodiesterase inhibitor IBMX and RO 20-1724, the cyclic AMP level increased from 39.2 to 73.3 and 285.5 pmol/mg protein, respectively. The high level obtained with RO 20-1724 could be inhibited by increasing concentrations of IBMX or by adenosine deaminase, but not by dipyridamole. 2-Chloroadenosine promoted a dose-dependent cyclic AMP accumulation in tecta incubated with RO 20-1724 and adenosine deaminase. This effect was blocked by IBMX and varied substantially during the development of the tissue. The degree of stimulation increased after day 11 of incubation, attaining maximal levels on day 14. The effect of 2-chloroadenosine remained constant until day 18, a period when both the protein content and the basal cyclic AMP levels are increasing in the developing tectum. The cyclic AMP increase elicited by 2-chloroadenosine was greatly reduced in tecta from 20-day-old embryos and 2-day-old chicks. The putative transmitters glutamate and glycine and the neurotransmitter analogs isoproterenol and carbachol had no stimulatory effect on the cyclic AMP accumulation of tecta from 10- and 17-day-old embryos.
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PMID:Development of adenosine-dependent cyclic AMP accumulation in the avian optic tectum. 244 20

Protein I is a neuronal phosphoprotein associated primarily with synaptic vesicles. Regulation of its state of phosphorylation has been investigated in slices of rat facial nucleus. This brainstem motor nucleus has a facilitatory serotonergic input and contains no interneurons. Serotonin (5-hydroxytryptamine, 5-HT, 10(-4) M), in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX, 4 x 10(-5) M), converted approximately 26% of Protein I in these slices from the dephospho-form to the phospho-form. This effect was partially inhibited using two classical 5-HT antagonists, mianserin added to the slices during in vitro incubation and metergoline administered in vivo. The effect of 5-HT appeared to be Ca2+-dependent, unlike that of IBMX (10(-3) M). Adenosine, its analog 2-chloroadenosine, and ATP also increased the phosphorylation of Protein I in facial nucleus slices. 2-Chloroadenosine (5 x 10(-4) M) caused a 29% phosphorylation of Protein I, and this effect was not dependent on extracellular Ca2+. The phosphorylation of Protein I caused both by 2-chloroadenosine and by ATP was inhibited by the adenosine antagonist 2'-deoxyadenosine. Results of additional experiments suggest that the great majority of the Protein I in the facial nucleus is present in presynaptic terminals other than the serotonergic afferents. It is concluded that the stimulation by 5-HT and adenosine of Protein I phosphorylation results largely from a direct action of these compounds on those Protein I-containing terminals.
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PMID:Neurotransmitter- and neuromodulator-dependent alterations in phosphorylation of protein I in slices of rat facial nucleus. 616 92

Adenosine stimulates the formation of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in rat spinal cord tissue slices in a concentration-dependent manner with maximal accumulation (30 pmol/mg of protein) at a concentration of 1 mM (Ec50 50 microM). 2-Chloroadenosine (EC50 1 microM) produced a maximal accumulation to 50 pmol/mg of protein. The adenosine antagonists, theophylline and isobutylmethylxanthine, block the increase, and the phosphodiesterase inhibitor, RO 20-1724, potentiates the increase in cyclic AMP accumulation. Adenosine deaminase eliminated the adenosine-dependent increase. Cyclic AMP accumulation was also enhanced by ATP, ADP and 5'-AMP. However, the stimulation due to these nucleotides was dependent upon conversion to adenosine. The increase in cyclic AMP accumulation was more than additive when adenosine was combined with norepinephrine. This potentiation effect is blocked by theophylline, isobutylmethylxanthine and alpha adrenergic antagonists. Additional experiments revealed that only postsynaptic alpha adrenergic agonists were capable of potentiating the response to adenosine. The interaction is concentration-dependent, is also observed with phosphorylated nucleotides of adenosine and is blocked specifically by alpha receptor antagonists. Receptor binding assays revealed that adenosine does not alter the number of alpha adrenergic receptors. Both the alpha receptor and adenosine-stimulated cyclic AMP accumulation were Ca++-dependent. These results suggest that adenosine-dependent cyclic AMP formation in rat spinal cord is mediated through two types of receptors, one of which is independent, and the other coupled to the alpha adrenergic receptor.
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PMID:Adenosine regulation of cyclic 3',5'-adenosine monophosphate formation in rat spinal cord. 627 Mar 5