Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary cultures, enriched in neurones or astroglial cells, from three phylogenetically different regions of the brain of the rat, the cerebral cortex, the striatum and the brain stem, were used to investigate the presence of opiate receptors, coupled to adenylate cyclase. Morphine was used as a mu-receptor agonist and [D-Ala2, D-Leu5]-enkephalin (DADLE) was used as a delta-receptor agonist. In the neuronal cultures, both ligands inhibited the prostaglandin (PG)E1-stimulated intracellular accumulation of cyclic AMP dose-dependently, with the most prominent effects seen in the cultures of striatum and with DADLE being more potent than morphine. The opiate receptor antagonist, naloxone reversed the effects. Morphine and DADLE, added together, inhibited the PGE1-stimulated accumulation of cyclic AMP, less than the sum of the effects of each drug. Therefore, it might be that these opioid receptors are localized together on the same neurone. Striatal neurones contained dopamine receptors coupled to cyclic AMP, as second messenger. It was shown that the D1 (dopamine) receptor-stimulated activity of adenylate cyclase was inhibited by the mu and delta opioid receptor ligands. Thus, interactions at the level of adenylate cyclase seem to exist between D1, mu and delta opiate receptors. In the astroglial enriched cultures, DADLE inhibited the PGE1-induced accumulation of cyclic AMP, however, with a less prominent effect in the brain stem cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Mu and delta opiate receptors in neuronal and astroglial primary cultures from various regions of the brain--coupling with adenylate cyclase, localisation on the same neurones and association with dopamine (D1) receptor adenylate cyclase. 166 98

The effects of mu, delta, and kappa receptor-agonists on forskolin stimulated cyclic adenosine-3',5'-monophosphate (cAMP) formation were examined in astroglial enriched primary cultures from the cerebral cortex of newborn rats. Intracellular cAMP accumulation was quantified by radioimmunoassay. Morphine was used as a mu-receptor agonist, D-Ala-D-Leu-Enkephalin (DADLE) as a delta-receptor agonist and dynorphin 1-13 (Dyn) as a kappa-receptor agonist. Basal cAMP levels were unaffected by either the opiate agonists or the antagonists used. In the presence of the cAMP stimulator forskolin, morphine had no significant effect on the cytoplasmic cAMP levels. DADLE caused a dose related inhibition of the forskolin stimulated cAMP accumulation. The effects of this delta receptor stimulation was blocked with the selective antagonist ICI 174.864. In the presence of Dyn, the forskolin stimulated cAMP accumulation was inhibited in a dose related manner. This kappa receptor stimulation was blocked with the selective antagonist MR 2266. Co-administration of DADLE and Dyn resulted in a non additive inhibition of the forskolin stimulated accumulation of cAMP. These findings indicate that astroglial enriched cultures from the cerebral cortex of rats express delta and kappa-receptors co-localized on the same population of cells, and that these receptors are inhibitory coupled to adenylate cyclase.
...
PMID:Delta and kappa opiate receptors in primary astroglial cultures from rat cerebral cortex. 198 60

Morphine, levorphanol and D-Ala2, Met enkephalin, but not bremazocine, pentazocine, U-50 488H and U-69 593, were found to inhibit adenylate cyclase activity dose-dependently in bullfrog brain membranes. The inhibition of the enzyme activity was abolished by naloxone. These results suggest that the signalling transduction of mu- and delta-agonists is partially mediated by the adenylate cyclase system coupled with opioid receptors, but that kappa-receptors may not be associated with adenylate cyclase.
...
PMID:Kappa-opioid agonists do not inhibit adenylate cyclase. 254 26

Carbachol (CCh)-stimulated hydrolysis of inositol lipids in human neuroblastoma SH-SY5Y cells was systematically characterized in parallel with the carbachol effects on cAMP formation. Carbachol concentration-dependently induced the hydrolysis of inositol lipids and formation of [3H]IP3, [3H]IP2 and [3H]IP1 in these cells labeled with [3H]inositol. The maximal amount of [3H]IP1 accumulated in the presence of 10 mM LiCl was about 50-fold above the basal level. The EC50 value of CCh was 14 microM. The muscarinic antagonists atropine, pirenzepine and 11-[[2-(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro- 6H-pyrido [2,3-b] (1,4)-benzodiazepine-6-one (AF-DX 116) competitively inhibited CCh-induced [3H]IP1 accumulation. The functional inhibition constants (converted from the pA2 values) were 0.24, 8.1 and 470 nM, respectively. These values are in good agreement with the inhibition constants of these drugs from antagonist/[3H]pirenzepine studies using intact cells. Forskolin, adenosine and PGE1 stimulated cAMP formation in this cell line. Morphine decreased PGE1-induced cAMP formation as well as the basal cAMP formation. However, CCh did not stimulate or inhibit the basal cAMP formation. Also, CCh did not have any effects on the adenosine and PGE1-induced cAMP formation in these cells. These data suggest that muscarinic M1 receptors are coupled to the hydrolysis of inositol lipids and not to the adenylate cyclase system in human neuroblastoma SH-SY5Y cells.
...
PMID:The coupling of muscarinic receptors to hydrolysis of inositol lipids in human neuroblastoma SH-SY5Y cells. 255 26

The effects of mu- and delta-preferring agonists on adenylate cyclase activity have been investigated in vitro in homogenates of guinea pig cochleas. Morphine, Leu-enkephalin, D-Ala2, N-methyl-Phe4, Gly-ol5-enkephalin (DAGO) and D-Ser2-Leu-enkephalin-Thr (DSLET) each inhibited the synthesis of cyclic AMP. This effect was reversed by naloxone which had a greater affinity in blocking the effect of the mu-preferring agonists (morphine, DAGO) than in blocking the effect of the delta-preferring agonists (Leu-enkephalin, DSLET). Finally, no additive effects were observed when various combinations of two agonists were used. These results indicate that opioid receptors exist in the guinea pig cochlea and that they are negatively linked to adenylate cyclase. The different affinities shown by naloxone to reverse the inhibition induced by the mu- and delta-preferring agonists suggest that morphine and DAGO act through mu-receptors, whereas Leu-enkephalin and DSLET act through delta-receptors. Since no additive effects have been found when combining two different agonists, it can be hypothesized that the mu- and delta-receptors are coupled to the same pool of adenylate cyclase. It may be proposed from these findings that in vivo enkephalins inhibit the synthesis of cyclic AMP via mu- and delta-receptors. However, whether this effect occurs at a presynaptic level (within opioid-containing olivocochlear varicosities) or at the postsynaptic level (within dendrites of the primary auditory neurons) remains to be determined.
...
PMID:Opioid receptors inhibit the adenylate cyclase in guinea pig cochleas. 282 9

Upon differentiation with retinoic acid of the human neuroblastoma cells SH-SY5Y into mature neurons, opioid drugs become highly effective in suppressing prostaglandin E1 (50% inhibition)- and forskolin (70% inhibition)-stimulated adenylate cyclase activity, which was assessed by measuring cyclic AMP accumulation in intact cells. Whereas the SH-SY5Y cells carry both mu and delta receptors in a ratio of mu/delta approximately equal to 5/1, the response is predominantly mediated by the mu receptor. Morphine acts as a strong agonist with an EC50 of 50 to 100 nM which falls into the therapeutic range expected for narcotic analgesic effects mediated by the mu receptor. Narcotic analgesic drugs with only partial agonism fail to evoke full response, which suggests that this cell model could provide a rapid screening assay for narcotic analgesic efficacy. Continued exposure of the cells to morphine resulted in partial tolerance within 12 hr with a 4-fold shift of morphine's EC50 to higher concentrations, whereas longer morphine exposure did not cause any further shift. Thus, the differentiated SH-SY5Y cells provide a suitable system for studying the molecular mechanisms of the narcotic analgesics.
...
PMID:Efficacy and tolerance of narcotic analgesics at the mu opioid receptor in differentiated human neuroblastoma cells. 283 42

The developmental profile of basal, NaF- and forskolin-stimulated adenylate cyclase [ATP-pyrophosphatelyase (cyclizing), EC 4.6.1.1] activity was established throughout the 21-day embryonic age of the chicken. The highest activities were observed from day 6 to day 8. Morphine inhibited NaF- and forskolin-stimulated brain adenylate cyclase activities only at days 6-8. The inhibition was not reversed by the antagonist naloxone, which also inhibited the enzyme during the same embryonic period and had no inhibitory effect thereafter. Thus, this action of morphine is not mediated through the conventional opiate receptor-adenylate cyclase system. We propose that the temporal specificity of this effect of morphine may play a role in the development of prenatal opiate effects.
...
PMID:An unconventional response of adenylate cyclase to morphine and naloxone in the chicken during early development. 287 54

Morphine (1-100 microM) was found to inhibit several concomitant events in brain slices and synaptosomes which are augmented by depolarizing agents. Thus, 45Ca2+ uptake, amino acid neurotransmitter release, increases in 3',5' cyclic AMP levels and 32Pi incorporation to proteins and lipids induced by veratrine (25 microM) and by potassium (56 mM), were each inhibited in a dose related manner. These inhibitory actions of morphine were all prevented by naloxone (1 microM). Evidence is presented that morphine binding to a receptor on the synaptic membrane affects intracellular mechanisms involved in neurotransmitter release possibly via a second messenger system. An enhancing action of GTP on the inhibitory influences of morphine suggests that its actions are mediated at least in part, via a coupling of the receptor to adenyl cyclase in the outer membrane. This is supported by its inhibitory action on the capacity of depolarizing agents to increase cyclic AMP levels.
...
PMID:Morphine inhibition of calcium fluxes, neurotransmitter release and protein and lipid phosphorylation in brain slices and synaptosomes. 287 8

Opioid receptors and enkephalinergic neurons in the central nervous system of Mytilus edulis have been reported. Also known is that the lateral epithelium of the gill is innervated by serotonergic, cilioexcitatory neurons and dopaminergic, cilioinhibitory neurons. The aim of the present report is to look for an effect of opioid agonists on the nervous control of the lateral cilia. Dopamine applied to the cerebral ganglion inhibited the activity of lateral cilia in the gill. This effect was blocked by the application of several opioids to the visceral ganglion. The block was reversed by the application of naloxone to the visceral ganglion. Dopamine applied to the visceral ganglion also inhibited lateral ciliary activity as shown earlier. Opioids applied to the visceral ganglion partially blocked this effect but this was overcome by higher concentrations of dopamine. Preparations with low endogenous rates of ciliary beating were stimulated by the application of opioids to the visceral ganglion. Naloxone blocked this effect. Preparations with high endogenous rates of ciliary beating were inhibited by the application of naloxone to the visceral ganglion. Electrical stimulation of the cerebrovisceral connective produced excitatory and inhibitory effects depending on the rate of stimulation. Morphine applied to the visceral ganglion diminished the cilioinhibitory effects and enhanced the cilioexcitatory effects of electrical stimulation. Morphine applied to the gill had no effect on the cilioinhibitory action of dopamine applied to the visceral ganglion. There was no observable effect of opioids applied to the gill and no alteration in the cilioinhibitory effect of dopamine or the cilioexcitatory effect of serotonin applied directly to the gill in the presence of opioids. Specific opioid binding sites were found in the visceral ganglion but were not found in gill, palp, mantle, or visceral mass tissue. A dopamine-stimulated adenylate cyclase activity was again found in the visceral ganglion and the gill. Etorphine reduced the dopamine stimulation of cyclase in the ganglion but not in the gill. It is postulated that a cilioinhibitory, dopaminergic mechanism includes nerves running from the cerebral ganglion to the gill with synaptic transmission in the visceral ganglion that can be modulated by opioids.
...
PMID:An opioid mechanism modulates central and not peripheral dopaminergic control of ciliary activity in the marine mussel Mytilus edulis. 301 5

The activity of adenylate cyclase in striatal membrane-enriched fractions (25,000 g) was inhibited by morphine, beta-endorphin, [D-Ala2-D-Leu5] enkephalin (DADLenk), fentanyl and bremazocine. Whereas guanosine triphosphate (GTP) appeared essential for the expression of this effect, sodium chloride seemed to enhance the degree of inhibition. Dopamine stimulation and sodium fluoride activation of the enzyme was also suppressed by morphine, beta-endorphin and DADLenk. beta-Endorphin and DADLenk inhibited adenylate cyclase activity in vasa deferentia membrane-enriched fractions (25,000 g); both opioids required GTP and NaCl and were inhibited by a delta-opioid receptor antagonist and by naloxone. Morphine, bremazocine and tifluadom did not significantly alter the activity of the vas deferens enzyme. Basal cyclic AMP values of striatal slices were not significantly altered by morphine, beta-endorphin or DADLenk. However, dopamine-induced elevation of cyclic AMP was reduced by morphine and this effect of the opiate was suppressed by naloxone. Only beta-endorphin lowered the basal cyclic AMP values in the vas deferens. The physiological relevance of adenylate cyclase coupling to opioid receptor subtypes is considered.
...
PMID:Opioid inhibition of adenylate cyclase in the striatum and vas deferens of the rat. 302 42


<< Previous 1 2 3 4 5 Next >>

---