CAMP accumulation activation

The H2 receptor is the second class of HA receptors. This is another G-protein-coupled receptor but, unlike the Hi receptor, the H2 receptor is coupled to adenylyl cyclase via the GTP-binding Gs protein (Hill et ah, 1997). Encoded by an intronless gene and located on human chromosome 5, the H2 receptor is made up of c. 358 amino acids (Gantz et ah, 1991 Traiffort et ah, 1995). Activation of the H2 receptor causes an accumulation of cAMP and activation of protein kinase A that eventually leads to the activation of cyclic-AMP-response element (CRE)-binding protein (CREB) (Hill et ah, 1997). In neurons, the H2 receptor mediates its excitatory effects by blocking the Ca2+-dependent K+ channel (Haas Konnerth, 1983). 

The effects of Li+ upon this system have been reviewed in depth by Mork [131]. Animal studies originally demonstrated that Li+ inhibits cAMP formation catalyzed by adenylate cyclase in a dose-dependent manner [132]. The level of cAMP in the urine of manic-depressive patients changes with mental state, being abnormally elevated during the switch period between depression and mania it is proposed that Li+ s inhibitory effect upon adenylate cyclase activity may correct this abnormality. Subsequent research, in accord with the initial experiments, have shown that Li+ s interference with this second messenger system involves more than one inhibitory action. At therapeutic levels, Li+ inhibits cAMP accumulation induced by many neurotransmitters and hormones, both in... 

Li+, at therapeutically relevant concentrations, is a potent inhibitor of norepinephrine-stimulated adenylate cyclase activity ex vivo in both rat [133] and human brain [134], and it inhibits norepinephrine-stimulated cAMP accumulation in Li+-treated patients. Li+ also inhibits dopamine-stimulated cAMP accumulation in rat brain [135]. These inhibitory effects of Li+ have been shown to be region specific within rat brain, a fact that has obvious significance for a therapeutic mechanism of action. It is interesting that other antimanic drugs may also have dampening effects on dopaminergic neurotransmission. 

Bioavailability of starch. Cooked rice was administered to colectomized rats by gastric intubation and the recovery of starch in the ileal digesta measured after 10 hours of ingestion. Significant starch (11-15%) was recovered from animals fed peas, lima beans, or kidney beans 0.2-0.4% of starch from rice. Oligosaccharide extraction, the size of the test meal, and the amount of starch did not affect starch biovailability . cAMP accumulation. Methanol extract of the grain, in cell culture at a concentration of 1 mg/mL, was active on mast cells " . 

The pupils become dilated and there are associated signs of hyperactivity of the sympathetic nervous system, such as hypertension and pilomotor stimulation. The mechanism(s) underlying tolerance and dependence are poorly understood. While acute activation of Gi/o-coupled receptors leads to inhibition of adenylyl cyclase, chronic activation of such receptors produces an increase in cAMP accumulation, particularly evident upon withdrawal of the inhibitory agonist. This phenomenon, referred to as adenylyl cyclase superactivation, is believed to play an important role in opioid addiction. 

The Di receptor is typically associated with the stimulation of adenylyl cyclase (Table 9-1) for example, Di-receptor-induced smooth muscle relaxation is presumably due to cAMP accumulation in the smooth muscle of those vascular beds in which dopamine is a vasodilator. D2 receptors have been found to inhibit adenylyl cyclase activity, open potassium channels, and decrease calcium influx. 

Receptor desensitization may also be mediated by second-messenger feedback. For example, adrenoceptors stimulate cAMP accumulation, which leads to activation of protein kinase A protein kinase A can phosphorylate residues on receptors, resulting in inhibition of receptor function. For the B2 receptor, phosphorylation occurs on serine residues both in the third cytoplasmic loop and in the carboxyl terminal tail of the receptor. Similarly, activation of protein kinase C by Gq-coupled receptors may lead to phosphorylation of this class of G protein-coupled receptors. This second-messenger feedback mechanism has been termed heterologous desensitization because activated protein kinase A or protein kinase C may phosphorylate any structurally similar receptor with the appropriate consensus sites for phosphorylation by these enzymes. 

ERK1/2 phosphorylation by involving G /o proteins, PKC and tyrosine kinase-dependent and -independent pathways. It has been found that Cl-IB-MECA produced a biphasic effect on cAMP accumulation with a stimulatory action starting at a concentration of 3 nM. This activity was triggered through PLC/PKC and not via direct Gs coupling (Germack and Dickenson 2004, 2005). 

As described previously, activation of P-adrenoreceptors leads to the accumulation of cAMP and activation of PKA. This suggests that the effects of NE and other P-adrenoreceptors agonists are mainly mediated via activation of PKA. This is supported by the fact, that the effects of NE is mimicked by P agonists or by compounds that increase... 

D-l Dopamine Receptor-Mediated Activation oi Adenylate Cyclase, cAMP Accumulation, and PTH Release in Dispersed Bovine Parathyroid Cells... 

When tested on osmotically-lysed bovine parathyroid cells, dopamine enhances the activity of adenylate cyclase, the enzyme converting ATP to cAKP (111. In comparison with its effect on cAMP accumulation, the effect of dopamine on adenylate cyclase activity is relatively modest, only a 2-fola increase in enzyme activity (Figure 7). Guanosine 5 -triphosphate (GTP) increases the stimulatory effect of dopamine in the presence of GTP, there is 3 to i<-fold stimulation of enzyme activity (11). 

In other cell types, guanine nucleotides interact with a guanine nucleotide subunit (G- or Ng-subunit) to translate receptor stimulation into increased adenylate cyclase activity (12.) Cholera toxin inhibits a specific GTPase on this guanine nucleotide subunit and thereby increases adenylate cyclase activity (13.). In dispersed cells from the bovine parathyroid gland, cholera toxin markedly increases cAMP formation and causes a 3 to 10-fold increase in the apparent affinity cf dopamine for its receptor (as determined by cAMP accumulation or IR-PTH secretion (J y.). The effects of guanine nucleotides and cholera toxin on cAMP accumulation in parathyroid cells result from interactions with the guanine nucleotide subunit in this cell. 

Effects of dopaminergic antagonists on dopamine-stimulated cAMP accumulation, adenylate cyclase activity, and calmodulin-stimulated phosphodiesterase (PDE) activity in intact bovine parathyroid cells or cellular homogenates. Values for or IC50 are given as uM. NT, not tested. 

ADTN and other dopamine agonists mimicked this effect which was antagonized by a- and B-flupenthixol, the a-isomer being 100 times more potent. In a similar way, dopamine caused a rapid 20-30-fold increase in cellular cAMP in dispersed bovine parathyroid cells. The potency of a series of dopaminergic agonists and antagonists on adenylate cyclase activity paralleled the effects of these ligands on CAMP accumulation and parathormone secretion (16). It was concluded that bovine parathyroid cells possess dopamine sites which are involved in the control of parathormone secretion. 

Secondly ergot derivatives which reveal a clearcut agonistic activity on prolactin secretion and as antiparkinson agents (20) were inactive on the cyclase. Surprisingly, lisuride and lergotrile were found to be weak antagonists of dopamine stimulated cAMP accumulation, but they could also antagonize the cAMP production stimulated by isoproterenol as... 

Figure 5. Comparison of the potency of isoproterenol in eliciting physiological and biochemical responses from the rat IL. Substantially lower concentrations of isoproterenol stimulate the release of IR-aMSH (aMSH) than are required to enhance cAMP accumulation by intact IL cells (cAMP), stimulate adenylate cyclase activity in cell-free homogenates of IL tissue (cyclase), or occupy the specific binding sites defined with IHYP (binding) (19).

For each response examined, inhibition of isoproterenol-stimulated cAMP accumulation by intact cells ( ) inhibition of basal release of IR-aMSH by intact cells ( J occupancy of specific [3H]-spiroperidol binding sites in a cell-free homogenate (Q) and inhibition of isoproterenol-stimulated adenylate cyclase activity in a cell-free homogenate (M), the effect achieved with the indicated concentration of apomorphine is expressed as a percentage of the maximal effect of apomorphine (33). 

As in the case of cAMP, activation of PKA during ischemia is potentially harmful, for example, causing phosphorylation and activation of the L-type Ca2+ channels, thereby promoting the harmful effects of Ca2+ influx into the cardiomyocyte (Tsien 1983 Bunemann et al. 1999) and hyperphosphorylation of the ryanodine receptor to liberate excess amounts of Ca2+, as may occur in heart failure (Marks 2003). The harmful effects of cAMP accumulation during ischemia may be due, at least in part, to activation of PKA. However, activation of PKA has also been linked... 

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