Cyclic AMP, production

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. 

Duman, R. and Enna, S. J. Modulation of receptor-mediated cyclic AMP production in brain. Neuropharmacology 26 981-986,1987. 

Pharmacology These agents are synthetic adrenocortical steroids with basic glucocorticoid actions and effects. Glucocorticoids may decrease number and activity of inflammatory cells, enhance effect of beta-adrenergic drugs on cyclic AMP production, inhibit bronchoconstrictor mechanisms, or produce direct smooth muscle relaxation. Inhaler use provides effective local steroid activity with minimal systemic effect. 

Correct answer = A. The addition of glucose causes cyclic AMP production to decrease. In the absence of cyclic AMP, the CAP protein cannot remain bound to its DNA binding site. An empty CAP binding site is not able to help RNA polymerase initiate transcription, so the rate of transcription decreases. Lower mRNA produc tion results in decreased P-galactosidase syn thesis. Because lactose is still present, the inducer (allolactose) remains bound to the repressor, which continues to be unable to bind to the operator. 

FIGURE 26-1 Mechanism of action of beta agonists on respiratory smooth muscle. Beta agonists facilitate bronchodilation by stimulating adenyl cyclase activity, which in turn increases intracellular cyclic AMP production. Cyclic AMP activates protein kinase, which appears to add an inhibitory phosphate group to contractile proteins, thus causing muscle relaxation and bronchodilation. 

One of the major sources of confusion around dopamine receptor originated with the idea that the increase of the cyclic AMP production by dopamine is a physiological effect of dopamine (2) starting from this viewpoint, it is not necessary to try to correlate the data obtained in vitro with physiological effects in vivo. In fact, the stimulation of cyclic AMP by dopamine is a biochemical effect for which one needs to find a physiological response in vivo. Just because an enzyme is stimulated or inhibited by a given neurotransmitter does not ipso-facto prove that such a process is involved in neurotransmission. As we will see further, numerous criteria must be fulfilled before an enzyme or a binding site may be called a receptor site. 

Weiss S, Sebben M, Kemp DE, Bockaert J. Serotonin 5-HTj receptors mediate inhibition of cyclic AMP production in neurons. Eur J Pharmacol 1986 120 227-230. 

Fig. 4. Action of thyroid hormones on cyclic AMP production and degradation in the adipocyte. The response of the adipocyte to different lipolytic hormones (/3 catecholamines, ACTH and glucagon) is under thyroid hormone control both at the level of the receptor-adenylate cyclase complex and at the level of the phosphodiesterase. T, also regulates the expression of several key lipogenic enzymes.

The inhibitory GTP binding protein (G ) which has been demonstrated in many different cell types is also present in Leydig cells. Evidence for this was obtained from studies with cultured Leydig cells in which it was shown that the inhibitory effects of arginine vasotocin on steroidogenesis could be abolished by pertussis toxin, which inactivates Gj via ADP ribosylation [9]. However, effects of LH with or without vasotocin were not reported. Similar studies with forskolin [10] demonstrated that low concentrations of this compound inhibited hCG-stimulated cyclic AMP production and this inhibition was prevented by pertussis toxin. Recently, direct evidence for the presence of Gj in rat Leydig cells has been obtained by the demonstration of a 41000 protein (aj) after [32P]ADP ribosylation [11]. 

In testis Leydig cells the LH stimulated cyclic AMP production was unaffected by lowering the extracellular calcium concentration [15]. However, three inhibitors of calmodulin all inhibited LH stimulated cyclic AMP production, indicating that there may well be a requirement for calcium. In swine granulosa cells, calcium deprivation suppressed the LH dose-dependent accumulation of cyclic AMP by 50% [29]. 

At low concentrations of cholera toxin, cyclic AMP production is stimulated in purified Leydig cells without any detectable change in steroidogenesis [5,6]. 

Isoproterenol can stimulate cyclic AMP production more than 10-fold in freshly isolated Leydig cells without any change in steroid production, whereas LH can stimulate steroid production more than 10-fold without any detectable change in cyclic AMP [33]. 

Leydig cells have shown however, that exposure to low levels of LH delivered as a 10 min pulse every 2 h does desensitize the steroidogenic response [77]. Desensitization of the LH-induced cyclic AMP production and internalization of the LH receptor does occur with testis Leydig cells in vitro at physiological concentrations of LH and these processes paradoxically may be necessary to maintain the normal physiological response of the Leydig cell to LH [78]. 

ACTH stimulates the synthesis of steroids by the cells of the adrenal cortex. The steroidogenic action of ACTH is mediated primarily by the intracellular messenger cyclic AMP acting via cyclic AMP-dependent protein kinase. The evidence for this is that (i) ACTH stimulates cyclic AMP production in intact adrenocortical cells and in plasma membrane preparations (ii) cyclic AMP analogues added to adrenocortical cells stimulate steroidogenesis to the same extent as ACTH and (iii) mutant adrenocortical cells with defective cyclic AMP-dependent protein kinase lack stimulation of steroidogenesis by ACTH [2],... 

Both type I and type II cyclic AMP-dependent protein kinase forms are found in the adrenal cortex [8]. The predominant form in the Y1 adrenocortical tumor cell line is type I [2], Yl(Kin) mutants with RI subunits which have a much lower affinity for cyclic AMP lack ACTH-stimulated cyclic AMP production, thus demonstrating the involvement of the type I form of cyclic AMP-dependent protein kinase in the action of ACTH. 

From the evidence accumulated so far, it seems likely that the cAMP signal transduction pathway will be a major effector of a stimulatory signal to the pars tuberalis, which can be regulated by melatonin [115]. The effect of aluminum as AlF41 has been studied on inositol phosphate accumulation, calcium mobilization, and cyclic AMP production in ovine pars tuberalis cells [116]. In the presence of 10 mmol L-1 LiCl, AlF41 stimulated the net accumulation of inositol phosphates over a 40-min incubation. Lithium is a known inhibitor of phosphatases in the inositol phosphate-recycling pathway. The results show the existence of a lithium-sensitive phosphoinositide signaling. 

Cardiac P -receptors mediate effects of sympathetic nerve stimulation. Cardiac Pj-receptors mediate effects of circulating adrenaline, when this is secreted at a sufficient rate, e.g. following a myocardial inforction or in heart feilure. Both receptors are coupled to the same intracellular signalling pathway (cyclic AMP production) and mediate the same biological effects. 

Bylund DB, Ray-Prenger C. a2A and a2B adrenergic receptor subtypes attenuation of cyclic AMP production in cell lines containing only one receptor subtype. J Pharmacol Exp Ther 1989 251 640-644. 

H. Okuda, C. Morimoto, and T. Tsuji-ta. Relationship between cyclic AMP production and lipolysis induced by forsko-lin in rat fat cells, J. Lipid Res., 1992, 33, 225-231. 

Response of the adenylate cyclase system to a hormone is determined by the types and amounts of various constituent proteins. Cyclic AMP production is limited by the amount of adenylate cyclase present. When all the adenylate cyclase is fully stimulated, further hormone binding to Rs s cannot increase the rate of cAMP synthesis. In cells having many different Rs s (adipocytes have them for epinephrine, ACTH, TSH, glucagon, MSH, and vasopressin), maximal occupancy of the receptors may not... 

Glycerol phosphorylation to prevent futile esterification of fatty acids Activation of cyclic AMP production by Insulin Hormone-sensitive lipoprotein lipase... 

Cannabinoid Receptor-Mediated Inhibition of Cyclic AMP Production. 56... 

Cannabinoid Receptor-Mediated Stimulation of Cyclic AMP Production. .. 57... 

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