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Ischemic Inhibition of Calcium Slow Current in the Heart
Published in Samuel Sideman, Rafael Beyar, Analysis and Simulation of the Cardiac System — Ischemia, 2020
A test of whether the regulatory effect of cAMP is exerted by means of the cAMP-dependent protein kinase and phosphorylation was made by intracellular injection of the catalytic subunit (protein) of the cAMP-dependent protein kinase. Such injections induced and enhanced the slow APs6 and potentiated Isi.12 Another direct test of the phosphorylation hypothesis was done by intracellular injection (by the liposome method) of an inhibitor (protein) of the cAMP-dependent protein kinase into cultured chick heart cells.6 It was found that the inhibitor depressed and abolished the slow APs (Figure 8). Although some depolarization also occurred concomitantly, it was shown that the slow channels were blocked at larger take-off potentials produced by application of repolarizing current pulses. The effect of the inhibitor was rapidly reversed by injection of the catalytic subunit of the cAMP-dependent protein kinase. Thus, these results further support the phosphorylation hypothesis.
Drugs of Abuse and Addiction
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Aarushi Singh
Opioids belong to the first class of mechanistic classification of drugs that is they act by activating GPCRs (Luscher et al., 2006). G-proteins, cAMP second messenger, and protein phosphorylation pathway mediate important aspects of opioids. Opioids increase dopamine concentration by acting on MORs which is manifested on GABA neurons of the VTA region. These MORs act with a dual action on these GABA neurons, first by hyperpolarising the GABA neurons this way the plasma membrane potential becomes more negative and action potential is never reached. Secondly, it decreases the release of GABA (Pickel et al., 2002; Luscher et al., 1997). Mediation of post-hyperpolarization is done by G-protein coupled inwardly rectifying K+ channels (GIRK). MORs inhibit Ca2+ channels and activate voltage-gated K+ channels (Pickel et al., 2002; Luscher et al., 1997; Vaughan et al., 1997; Johnson and North, 1992). Opioids also act on the locus coeruleus (LC) which is the largest nonadrenergic nucleus in brain. Opioids decrease firing rate of LC neurons by activation of inward rectifying K+ channels and inhibition of slowly depolarizing cation channel as you can see in Figure 20.6 and Figure 20.7. Both actions occur through G-proteins. cAMP levels of neurons are reduced and cAMP-dependent protein kinase is activated. Adenylate cyclase activity is acutely reduced in LC (Aghajanian, 1978; Andrade et al., 1983; Wang and Aghajanian, 1990; Alreja and Aghajanian, 1991).
Site-Selective cAMP Analogs in the Arrest of Cancer Cell Growth
Published in Robert I. Glazer, Developments in Cancer Chemotherapy, 2019
The cAMP-dependent protein kinase is usually present in tissues as a mixture of type I and type II isozymes.6,11 Both isozymes contain dimeric R subunits and two C subunits.6,11 The R subunits of type I and type II protein kinase differ with respect to various physioochemical and immunological properties, whereas C subunits are identical. The R subunit of type I kinase (RI) characterizied in all mammalian species has a uniform molecular weight of 48,000.11 The R subunit of type II kinase (RII) has been shown to exhibit microheterogeneity; 50,000 to 56,000 mol wt RII species have been identified in various tissues.21,22
Effects of cinnamaldehyde on glucose-6-phosphate dehydrogenase activity, some biochemical and hematological parameters in diabetic rats
Published in Biomarkers, 2022
Remzi Çelik, Handan Mert, Bahat Comba, Nihat Mert
Xu et al. (2005) reported that chronic hyperglycaemia inhibited G6PD activity by decreased expression and increased phosphorylation of G6PD. High glucose leads to an increase in cAMP in various cells such as Islets of pancreas (Zawalich et al.1975), adipose tissue (Jackowski et al.1978), bovine aortic endothelial cells (Zhang et al.2000), and human microvascular endothelial cells (Kamal et al.1998). High levels of glucose in endothelial cells have been shown to stimulate the activation of cAMP dependent protein kinase A (PKA) and inhibit G6PD activity (Asahina et al.1995). Liver G6PD activity is reduced in cases of hypoinsulinism (hunger, diabetes). When hungry animals are re-fed, insulin is synthesised again. The activity of this enzyme reaches high levels. Insulin injection, followed by feeding, results in increased G6PD (Weber and Convery 1966).
Anti-melanogenic effects of extracellular vesicles derived from plant leaves and stems in mouse melanoma cells and human healthy skin
Published in Journal of Extracellular Vesicles, 2020
Ruri Lee, Hae Ju Ko, Kimin Kim, Yehjoo Sohn, Seo Yun Min, Jeong Ah Kim, Dokyun Na, Ju Hun Yeon
α-Melanocyte-stimulating hormone (α-MSH) binds to MC1R (melanocortin-1 receptor) on the cell surface and activates adenylate cyclase, which leads to an elevated level of intracellular cyclic AMP (cAMP). cAMP is mediated through cAMP-dependent protein kinase A which results in the phosphorylation of cAMP response element-binding protein (CREB). Activated CREB induces MITF, which is expressed in melanocytes and is known to play a critical role in the differentiation and development of melanocyte. MITF regulates tyrosinase-related protein (TRP) family, which are multienzyme complexes including tyrosinase (TYR), Tyrp1 (TRP1) and Dct (TRP2). TYR activity is more stable in the presence of TRP-1 and TRP-2, and TYR is coexpressed with TRP1 or TRP2 by the regulation of MITF in melanoma cells [25]. TRP1 is a necessary enzyme for the correct trafficking of TYR to melanin synthesis, and TRP2 plays an important role in TRP catalytic activity in the early stages in melanin synthesis. All three interact with one another in melanoma cells (Supplementary Figure S1) [26–31].
Erythrocyte cAMP in Determining Frequency of Acute Pain Episodes in Sickle Cell Disease Patients from Odisha State, India
Published in Hemoglobin, 2019
Bimal P. Jit, Pradeep K. Mohanty, Avinash Pradhan, Prasanta Purohit, Kishalaya Das, Siris Patel, Satyabrata Meher, Shalini Sinha, Jyoti R. Mohanty, Rajendra Kumar Behera, Padmalaya Das
Episodes of VOC are more frequent during conditions of stress such as vigorous physical activity, fever, surgical stress, etc. Stress hormone epinephrine released during stress possibly contributes toward initiation and/or exacerbation of vaso-occlusion. Epinephrine promotes vaso-occlusion, which is mediated through the erythrocyte second messenger, the cyclic adenosine monophosphate (cAMP). Stimulation of the β2-adrenergic receptor (β2-AR) activates the G-protein coupled receptor (GPCR), which in turn stimulates membrane bound adenyl cyclase to convert adenosine triphosphate (ATP) to cAMP [7–9]. The cAMP up-regulates the cAMP-dependent protein kinase A (PKA) pathway, one of the most well-studied signaling pathways in RBCs [10,11]. Up-regulation of PKA pathway activates the sickled RBC membrane proteins and increases their adhesion to endothelial cells and leukocytes [12]. Sickled RBCs contain higher concentrations of cAMP than normal RBCs even at basal conditions, while epinephrine further widens this difference [12,13]. Hydroxyurea (HU) reduces frequency of VOCs by increasing Hb F levels that decreases Hb S polymerization. However, clinical improvement is often noticed before significant rise in Hb F concentration. The acute protective effect of this drug is reported to be mediated through decreasing intracellular cAMP levels and diminished expression and activation of RBC membrane receptors and reduced cell adhesion [14,15]. Epinephrine stimulation has insignificant effect on cell adhesion in HU-treated patients [16].