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)

1. Interlobular ducts were isolated from the rat pancreas and maintained in short-term tissue culture. Fluid secretion from these isolated ducts was measured using micropuncture techniques, intracellular calcium concentration ([Ca2+]i) by fura-2 microspectrofluorimetry, and cyclic AMP by radioimmunoassay. 2. Applying secretin and ACh simultaneously to ducts caused either a stimulation or an inhibition of fluid secretion depending on the doses employed. 3. The inhibitory effect of secretin and ACh could be relieved by atropine, and by the protein kinase C (PKC) inhibitors staurosporine and 1-(5-isoquinolinylsulphonyl)-2-methyl-piperazine (H-7). 4. Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol 12, 13-dibutyrate (PDBu) inhibited secretin-evoked fluid secretion. 5. ACh and TPA also inhibited fluid secretion stimulated by the adenylate cyclase activator, forskolin. 6. Neither secretin nor the PKC activators and inhibitors had any effect on either the increase in [Ca2+]i evoked by ACh or the increase in intracellular cyclic AMP evoked by secretin and forskolin. 7. We conclude that the inhibitory effect of combined doses of secretin and ACh on ductal fluid secretion is probably mediated by PKC at a point in the secretory mechanism distal to the generation of intracellular messengers.
...
PMID:Interactions between secretin and acetylcholine in the regulation of fluid secretion by isolated rat pancreatic ducts. 891 Feb 14

At the neuromuscular junction and possibly also at the synaptic level in the brain, the main sequence of events (see Fig. 5) that involves purines in modulation of ACh release includes the following observations: (1) storage of ATP and its release either together with, or independently of acetylcholine. ATP is also released from the post-junctional component. Adenosine as such is released either from the motor nerve terminals or from the post-junctional component. (2) There is extracellular hydrolysis of ATP to adenosine, which is the active substance to modulate transmitter release. The key enzyme in the conversion of AMP into adenosine is the ecto 5'-nucleotidase. When ecto-5'-nucleotidase is not available (e.g. in cholinergic nerve terminals of the cerebral cortex) ATP as such exerts the neuromodulatory role normally fulfilled by adenosine. (3) Both the inhibition and the excitation induced by adenosine on ACh release in the rat is inactivated through up-take and deamination. (4) Adenosine-induced inhibition of ACh release is mediated via A1 receptors and the excitation via A2a receptors. The A2a receptors are positively coupled to the adenylate cyclase/cyclic AMP system, whereas the presynaptic A1 receptors (a) may be negatively linked to adenylate cyclase and (b) to phospholipase C, and, upon stimulation, (c) increase potassium conductance and (d) decrease calcium conductance. (5) Activation of A2a receptors is essential for substances that facilitate ACh release (e.g. CGRP, forskolin) to exert their effects, as well as for induction of nicotinic autofacilitatory receptor desensitization. (6) There are interactions between A1 and A2a receptors. Thus, the net adenosine neuromodulatory response is the resultant, at each moment, of the relative degree of activation of each one of these receptors. This relative activation depends upon the intensity (frequency, pulse duration) of stimulation of the motor nerve terminals. (7) Adenosine released as such seems to preferentially activate A1 receptors, whereas the adenosine formed from metabolism of adenine nucleotides prefers to activate the A2a receptors. In conclusion, to find out precisely what occurs with ACh in transmitting its message at the synaptic level, one has to consider the subtle ways used by purines to modulate the ACh response. It therefore appears of interest that pharmacological and therapeutic strategies use this knowledge to approach cholinergic transmission deficiencies based upon reduction of ACh release.
...
PMID:Purinergic regulation of acetylcholine release. 900 12

Acutely dissociated adult rat striatal cholinergic neurons labeled with [3H]choline were used in a perifusion system to study muscarinic regulation of basal and forskolin-stimulated fractional [3H]acetylcholine ([3H]-ACh) efflux in the absence of synaptic modulation. Carbachol inhibited basal (40% maximal inhibition; IC50 approximately 0.7 microM) and forskolin-evoked release (75% inhibition; IC50 approximately 0.05 microM) in a concentration-dependent manner, and both carbachol actions were abolished with atropine. Thus, activation of striatal muscarinic cholinergic autoreceptors potently inhibits basal and adenylate cyclase-stimulated ACh release. Tonic inhibitory control of cholinergic activity by functional striatal circuitry apparently prevents detection of these important physiological interactions in slices or in situ.
...
PMID:Carbachol inhibits basal and forskolin-evoked adult rat striatal acetylcholine release. 922 66

1. The regulation of cardiac Cl- current (ICl) by tyrosine and serine/threonine phosphorylation was examined in guinea-pig and rat ventricular myocytes. The protein tyrosine kinase (PTK) inhibitor genistein (GST) and phosphotyrosine phosphatase (PTP) inhibitor sodium orthovanadate (VO4) were used to modify tyrosine phosphorylation, whereas forskolin (FSK), cAMP, and other agents were used to modify cytoplasmic cAMP concentration and protein kinase A (PKA) phosphorylation. 2. Low concentrations (0.1 microM) of FSK did not activate the PKA-regulated cystic fibrosis transmembrane regulator (CFTR) ICl in guinea-pig ventricular myocytes, but strongly potentiated activation of an ICl by 20-100 microM GST. The potentiation did not occur when GST was replaced by PTK-inactive daidzein, and it was strongly inhibited by 1 mM VO4. 3. Potentiation by 0.1 microM FSK was linked to a small stimulation of the adenylate cyclase-cAMP-PKA pathway. The potentiation was not mimicked by inactive 1,9-dideoxyforskolin, and was inhibited by muscarinic stimulation (ACh) and by a PKA inhibitor. Internal application of a cAMP solution that alone was too weak to activate CFTR ICl strongly potentiated the activation of ICl by 50 microM GST and occluded potentiation by 0.1 microM FSK. 4. The foregoing suggests that potentiated ICl flows through cAMP-dependent CFTR channels. In agreement with this interpretation, GST did not increase ICl when CFTR was maximally activated by a high concentration (5 microM) of FSK and okadaic acid, and neither GST nor GST plus FSK activated an ICl in CFTR-deficient rat myocytes. The lack of effect in rat myocytes was not due to the absence of functional, channel-relevant PKA and PTK-PTP systems, because (as in guinea-pig myocytes) L-type Ca2+ current (ICa,L) was stimulated by FSK and inhibited in a VO4-reversible manner by GST. 5. The synergistic activation of CFTR by low concentrations of FSK and GST cannot be explained by either a GST-induced elevation of cAMP concentration or inhibition of serine/threonine phosphatase. Rather, it appears to be due to tyrosine dephosphorylation that facilitates PKA-mediated phosphorylation of the channels.
...
PMID:Synergistic activation of guinea-pig cardiac cystic fibrosis transmembrane conductance regulator by the tyrosine kinase inhibitor genistein and cAMP. 940 69

Changes in acetylcholine secretion in the cholinergic synapses of the rat cerebral hemispheres and brain stem were studied in in vivo experiments against the background of modulation of the activity of the adenylate cyclase and phosphoinositide secondary messenger systems by injection of caffeine and lithium chloride. The level of mediator secretion was determined according to the content of bound acetylcholine fractions in the homogenate of the indicated parts of the animal's brain. It was established that secretion of the mediator in the rat hemispheres is regulated by postsynaptic N-cholinoceptors located on the body of cholinergic neurons which have a phosphoinositide system actiung as secondary mediators and, possibly are related to subtype M1. It is also possible that the secretion is also regulated by presynaptic autoreceptors connected with the adenylate cyclase system, which function according to the mechanism of negative feedback and is related to subtype M2. Acetylcholine secretion in the brain stem synapses is regulated according to the negative feedback mechanism by muscarine receptors linked with the adenylate cyclase system and probably related to subtype M4.
...
PMID:[The role of adenylate cyclase and phosphoinositide second messenger systems in regulation of acetylcholine secretion in synapses of the cerebral hemispheres and brain stem in rats]. 946 May 86

Bicarbonate excretion in bile is a major function of the biliary epithelium. It is driven by the apically located Cl-/HCO3- exchanger which is functionally coupled with a cAMP-dependent Cl- channel (CFTR). A number of hormones and/or neuropeptides with different mechanisms and at different intracellular levels regulate, in concert, the processes underlying bicarbonate excretion in the biliary epithelium. Secretin induces a bicarbonate rich choleresis by stimulating the activity of the Cl-/HCO3- exchanger by cAMP and protein kinase A mediated phosphorylation of CFTR regulatory domain. Protein phosphatase 1/2A are involved in the run-down of secretory stimulus after secretin removal. Acetylcholine potentiates secretin-choleresis by inducing a Ca(++)-calcineurin mediated "sensitization" of adenyl cyclase to secretin. Bombesin and vasoactive intestinal peptide also enhance the Cl-/HCO3- exchanger activity, but the intracellular signal transduction pathway has not yet been defined. Somatostatin and gastrin inhibit basal and/or secretin-stimulated bicarbonate excretion by down-regulating the secretin receptor and decreasing cAMP intracellular levels induced by secretin.
...
PMID:Hormonal regulation of bicarbonate secretion in the biliary epithelium. 962 62

The effect of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide-38 (PACAP-38), and PACAP-27 on the release of serotonin (5-HT) into the intestinal lumen and the portal circulation was studied by using in vivo isolated vascularly and luminally perfused rat duodenum. 5-HT levels were determined by HPLC. VIP, PACAP-38, and PACAP-27 reduced the luminal release of 5-HT but did not affect the vascular release of 5-HT. The inhibitory effect caused by VIP, PACAP-38, and PACAP-27 was not affected by either atropine, hexamethonium, TTX, or TTX plus ACh, but it was completely antagonized by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). The VIP receptor antagonist VIP-(10-28) blocked the effects of VIP, PACAP-38, and PACAP-27. These results suggest that VIP and PACAP exert a direct inhibitory effect on the luminal release of 5-HT from the enterochromaffin (EC) cells via a common receptor site on the EC cells and that this effect is mediated by NO but not by cholinergic pathways. A single injection of TTX, atropine, or hexamethonium reduced the luminal release of 5-HT, whereas a single injection of VIP-(10-28) stimulated the luminal release of 5-HT and this effect was antagonized by atropine, hexamethonium, or TTX. These results suggest that EC cells may receive the direct innervation of cholinergic neurons as well as VIP and/or PACAP neurons, with the former exerting a tonic stimulatory influence and the latter exerting a tonic inhibitory influence on 5-HT release into the intestinal lumen.
...
PMID:Effect of VIP and PACAP on basal release of serotonin from isolated vascularly and luminally perfused rat duodenum. 975 4

The effects on acetylcholine-induced membrane currents (ACh currents), produced by agents known to modify the activity of intracellular messengers, were studied in the neurons of the guinea-pig ileum submucous plexus (SMP) using a whole-cell patch clamp recording method. The ACh currents were not affected by forskolin, the adenylate cyclase activator, regardless of whether or not ATP and GTP were present in the intracellular solution, and by phorbol 12-myristate 13-acetate, the protein kinase C activator. The ACh currents were strongly suppressed by thapsigargin, the microsomal calcium ATPase inhibitor, and genistein, the tyrosine protein kinase inhibitor. They were also suppressed by 3-isobutyl-1-methylxanthine, the cyclic-AMP phosphodiesterase inhibitor, regardless of the presence of forskolin in the extracellular solution and ATP and GTP in the intracellular solution. In addition, the currents were suppressed by activation of P2 purinoceptors with ATP, which could not be explained by a direct effect of ATP on nicotinic acetylcholine receptors (nAChRs). Reactive blue 2, the P2y purinoceptor antagonist, did not abolish inhibition of the ACh current by ATP. Alpha,beta-Imido-ATP and adenosine caused no membrane current responses and did not influence the ACh currents. These results suggest that the activity of the nAChRs in the SMP neurons is strongly suppressed by raised intracellular Ca2+ level, without involvement of protein kinases A and C, and may involve the participation of tyrosine kinase. The activity of nAChRs is also influenced by the activity of P2 purinoceptors; the mechanisms responsible for this influence are not yet clear. So, the activity of the SMP neuronal nAChRs is relatively independent on the intracellular signaling known to influence many other groups of transmitter-gated receptors of neuronal membrane.
...
PMID:Modulation of nicotinic acetylcholine receptor activity in submucous neurons by intracellular messengers. 993 65

1. We hypothesized that acetylcholine would attenuate the metabolic effect of increasing cAMP and decreasing cGMP on cardiac myocyte O2 consumption (VO2) in dog, and this effect would be altered in left ventricular hypertrophy (LVH) produced by aortic valve placation. 2. Steady-state VO2 of a suspension of ventricular myocytes from control (n = 7) and LVH (n = 6) dogs was measured by Clark O2 electrodes during electrical stimulation (5 ms, 1 Hz, in 2 mm Ca2+). Cyclic AMP and cyclic GMP were determined by radioimmunoassay. Cellular cAMP was increased by forskolin (adenylate cyclase stimulator) and cGMP was decreased by LY83583 (guanylate cyclase inhibitor) both at 10(-7,-6,-5,-4) M with and without 10(-6) M acetylcholine. 3. Baseline cGMP level in LVH (62 +/- 10 fmol 10(-5) myocytes) was significantly greater than that in control (20 +/- 3), although the myocyte VO2 (356 +/- 39 nL O2 min(-1) 10(-5) myocytes) and cAMP levels (3.9 +/- 0.6 nmol 10(5-1) myocytes) were similar to control (312 +/- 23 and 6.9 +/- 3.1). 4. Forskolin increased myocyte cAMP in both control and LVH myocytes and increased VO2 by 51 +/- 13 in control and 91 +/- 65 in LVH myocytes. LY83583 decreased myocyte cGMP levels in control and LVH myocytes and increased VO2 by 128 +/- 57 in control and 43 +/- 26 in LVH myocytes. 5. Acetylcholine altered the cAMP, cGMP, and VO2 levels in control to 2.4 +/- 0.4, 30 +/- 3 and 213 +/- 27 and LVH to 2.5 +/- 0.3, 85 +/- 9 and 261 +/- 32. Acetylcholine attenuated the maximal effects of forskolin on VO2 to 32 +/- 27 in control and 66 +/- 56 in LVH myocytes. Acetylcholine also decreased the maximal effects of LY83583 to 82 +/- 50 in control and 19 +/- 19 in LVH myocytes. 6. The positive metabolic effects of both increases in myocyte cAMP and decreases in cGMP were blunted by acetylcholine. There was a significant increase in myocyte cGMP with forskolin in LVH myocytes. Acetylcholine decreased the increased myocyte VO2 caused by elevated cAMP or decreased cGMP in both control and LVH myocytes, although the absolute decrease in cAMP was reduced and the absolute values of cGMP were higher in LVH myocytes.
...
PMID:Altered effects of acetylcholine on cyclic AMP and GMP induced changes in O2 consumption of hypertrophic dog cardiac myocytes. 1038 66

Acetylcholine is an important regulator of local cerebral blood flow. There is, however, limited information available on the possible sites of action of this neurotransmitter on brain intraparenchymal microvessels. In this study, a combination of molecular and functional approaches was used to identify which of the five muscarinic acetylcholine receptors (mAChR) are present in human brain microvessels and their intimately associated astroglial cells. Microvessel and capillary fractions isolated from human cerebral cortex were found by reverse transcriptase-polymerase chain reaction to express m2, m3, and, occasionally, m1 and m5 receptor subtypes. To localize these receptors to a specific cellular compartment of the vessel wall, cultures of human brain microvascular endothelial and smooth muscle cells were used, together with cultured human brain astrocytes. Endothelial cells invariably expressed m2 and m5 receptors, and occasionally the m1 receptor; smooth muscle cells exhibited messages for all except the m4 mAChR subtypes, whereas messages for all five muscarinic receptors were identified in astrocytes. In all three cell types studied, acetylcholine induced a pirenzepine-sensitive increase (62% to 176%, P<0.05 to 0.01) in inositol trisphosphate, suggesting functional coupling of m1, m3, or m5 mAChR to a phospholipase C signaling cascade. Similarly, coupling of m2 or m4 mAChR to adenylate cyclase inhibition in endothelial cells and astrocytes, but not in smooth muscle cells, was demonstrated by the ability of carbachol to significantly reduce (44% to 50%, P<0.05 to 0.01) the forskolin-stimulated increase in cAMP levels. This effect was reversed by the mAChR antagonist AFDX 384. The results indicate that microvessels are able to respond to neurally released acetylcholine and that mAChR, distributed in different vascular and astroglial compartments, could regulate cortical perfusion and, possibly, blood-brain barrier permeability, functions that could become jeopardized in neurodegenerative disorders such as Alzheimer's disease.
...
PMID:Functional acetylcholine muscarinic receptor subtypes in human brain microcirculation: identification and cellular localization. 1041 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---