CAMP production

Transfected cell systems with high expression levels Coupling to Gs, stimulation of cAMP production ... 

The VACM-1 receptor is a membrane-associated protein with a single putative transmembrane domain that binds selectively AVP (XD — 2 nM), but cannot discriminate between VXR and V2R analogues. It is expressed in endothelial and medullary collecting duct cells and upon stimulation by AVP. It induces a mobilization of cytosolic-free Ca2+, decreases cAMP production and inhibits cellular growth via MAPK phosphorylation and p53 expression. The mechanism of action and physiological functions of this new receptor are not well understood, but it seems to participate in the regulation of AVP induced signal transduction pathways or of a yet unidentified peptide. 

The M2 and M4 receptors also show struetural similarities. Through G-protein (Gi) they inhibit cyclic AMP production and open K+ ehannels while activation of another G-protein (Go) closes Ca + channels. The latter effeet will cause membrane hyperpolarisation as will the Gpinduced inerease in K+ efflux. The reduction in cAMP production, although possibly leading to depolarisation, is more likely to explain the presynaptie reduction in ACh release assoeiated with the M2 receptor. 

When tested on prolactin release in isolated mammatrophs of bovine anterior pituitary, apomorphine appeared a full agonist (inhibiting release) while antagonism of the inhibition of prolactin release by the neuroleptics showed a potency more similar to that for binding than for blocking cAMP production. Also the inhibition of prolactin... 

The exact process(es) by which a2-adrenoceptors blunt release of transmitter from the terminals is still controversial but a reduction in the synthesis of the second messenger, cAMP, contributes to this process. a2-Adrenoceptors are negatively coupled to adenylyl cyclase, through a Pertussis toxin-sensitive Gi-like protein, and so their activation will reduce the cAMP production which is vital for several stages of the chemical cascade that culminates in vesicular exocytosis (see Chapter 4). The reduction in cAMP also indirectly reduces Ca + influx into the terminal and increases K+ conductance, thereby reducing neuronal excitability (reviewed by Starke 1987). Whichever of these releasecontrolling processes predominates is uncertain but it is likely that their relative importance depends on the type (or location) of the neuron. 

Figure 8 Forskolin-stimulated cAMP production of CHO At cells after addition of CPA in the absence ( ) or presence ( ) of 1 0 pM PD81,723.

The 5-HTy receptor is part of the G-protein superfamily of receptors, which contains seven transmembrane regions, and its stimulation leads to an increase in cAMP production (Thomas Hagan, 2004). The 5-HT7 receptor is expressed in a number of telencephalic, diencephalic, mesencephalic, and rhombencephalic areas (Table 9.8). 

The cellular mechanism of action of hydrocortisone, a glucocorticoid, is also related to proteins but not by the enhancement of cAMP production. Hydrocortisone is transported by simple diffusion across the membrane of the cell into the cytoplasm and binds to a specific receptor The steroid-receptor complex is activated and enters the nucleus, where it regulates transcription of specific gene sequences into ribonucleic acid (RNA). Eventually, messenger RNA (mRNA) is translated to form specific proteins in the cytoplasm that are involved in the steroid-induced cellular response. 

At present it is not known if all H3 receptor isoforms similarly activate the wide array of signaling pathways. In transfected cells, the rat H3(413) and H3(397) isoforms both inhibit adenylate cyclase more efficiently than does the hill length rat H3 receptor isoform (445 amino acids), but the former are less efficient in activating the MAPK pathway. Much less information is available for the human H3 receptor isoforms but shorter isoforms seem to couple more efficiently to G -proteins to inhibit cAMP production in transfected cells [40],... 

Sanders Did you ever look to see whether indomethacin (i.e. prostaglandin inhibition) decreases coupling between these Ca2+ waves and activation of BK channels Perhaps this is your time delay. Production of prostaglandin should activate protein kinase A because of cAMP production, and this will increase BK open probability. 

Agents that stimulate elevations in cAMP production also inhibit PLD activation. Thus, it may be that phosphorylation by protein kinase C can activate PLD, whereas phosphorylation at other sites on the enzyme by PKA can inhibit its activity. 

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

G, alpha Insertions/dele- syndrome fibrous dysplasia of bone cafe-au-lait skin lesions sexual precocity pituitary, thyroid, or adrenal tumors Albright s hereditary with constitutive cAMP production Inactivating G a (86-89)... 

The GRK4 SNPs include Arg65Len, Alal42Val, and Ala486Val. Dopamine D, receptor-mediated cAMP production is reported to be markedly impaired by these variants. Expression of these SNPs is also associated with increased basal phosphorylation of the dopamine Dj receptor. This suggests that increased basal phosphorylation of the dopamine Dj receptor by GRK4 may be associated with the decreased responsiveness of the dopamine Dj receptor in hypertension (187,188). 

The third group is that of compounds which may potentially be transported by the PTS and inhibit cAMP production. Cellulase synthesis is initiated after these compounds are consumed for cell growth. This group includes D-glucose, D-fructose, maltose, mannitol, glycerol, sorbitol, and -methyl glucoside. The presence of these compounds in Solka Floe fermentations, enhanced enzyme yields (132 to 254%) but the time required to complete cellulase synthesis took longer (106 to 148%) than the control. 

Cardiostimulation. By stimulating Pi-receptors, hence activation of ade-nylatcyclase (Ad-cyclase) and cAMP production, catecholamines augment all heart functions, including systolic force (positive inotropism), velocity of shortening (p. clinotropism), sinoatrial rate (p. chronotropism), conduction velocity (p. dromotropism), and excitability (p. bathmotropism). In pacemaker fibers, diastolic depolarization is hastened, so that the firing threshold for the action potential is reached sooner (positive chronotropic effect, B). The cardiostim-ulant effect of p-sympathomimetics such as epinephrine is exploited in the treatment of cardiac arrest Use of p-sympathomimetics in heart failure carries the risk of cardiac arrhythmias. 

Autonomic receptors further regulate calcium influx through the sarcolemma (Fig. 15.1). (3-Adrenergic stimulation results in the association of a catalytic subunit of a G protein coupled to the (3-receptor. This stimulates the enzyme adenylyl cyclase to convert ATP to cyclic adenosine monophosphate (cAMP). Increasing cAMP production results in a cAMP-dependent phosphorylation of the L-type calcium channel and a subsequent increase in the probability of the open state of the channel. This translates to an increase in transsarcolemmal calcium influx during phase 2 (the plateau phase) of the cardiac muscle action potential. The effects of transient increases in intracellular levels of cAMP are tightly con-... 

The Dj-dopaminergic receptor decreases cAMP production by inhibiting dopamine-sensitive adenylyl cyclase and opens channels but can also block Ca++ channels. It is located both presynaptically and postsyn-aptically on neurons in the caudate putamen, nucleus accumbens, and olfactory tubercle. Another member of this family is the Dj-receptor, which also decreases... 

G, Adenylyl cyclase-catalyzed cAMP production Brain, stomach, smooth muscle, heart, mast cells Arpromidine, impro-midine, amthamine, dimaprit Cimetidine, ranitidine, famotidine... 

Less is known about GABAg receptor structure. GABAg receptors are coupled indirectly to K+ channels. These receptors, which are always inhibitory, are coupled to G-proteins. When activated, GABAg receptors decrease Ca + conductance and inhibit cAMP production. The GABA, receptor is probably little more than a subtype of the GABA receptor. It contains the p subunit peptide and is located primarily, if not exclusively, in the retina. 

The primary effect of ACTH seems to be mediated via cAMP production by interaction of the hormone with differing populations of receptors. The difference between the extent of steroidogenesis and cAMP formation indicates different receptor affinities in different organs. 

Since they are linked to G-proteins, opioid receptors affect intracellular Ca and protein phosphorylation. Another principal biochemical effect of opiates is the inhibition of adenylate cyclase (AC), which decreases cAMP production. 

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