Neuroendocrine Factors
Michael H. Stone, Timothy J. Suchomel, W. Guy Hornsby, John P. Wagle, Aaron J. Cunanan in Strength and Conditioning in Sports, 2023
Activation of the effector element (enzyme or a calcium channel) creates a second messenger and results in a cascade effect. Guanine nucleotide-binding proteins (G proteins), are embedded in the cell membrane and contain alpha, beta, and gamma subunits. These regulate the activity of enzymes or calcium channels important for second messenger production. Based on current knowledge, two primary second messenger systems can be activated: cAMP and Ca++/IP3 (Figure 3.1a, b). G-protein activation of the enzyme adenyl cyclase results in cAMP formation; in the Ca++/IP3 system, the G protein simultaneously activates inositol triphosphate (IP3) formation and opens Ca++ channels. The cAMP and Ca++/IP3 systems are complementary in some cells but can have opposite effects in other tissues (23, 108). For example, for liver glycogenolysis the effect is complementary, but contraction and relaxation of smooth muscle can require different second messengers. A third type of second messenger, cyclic guanosine monophosphate (cGMP), has been established in a few tissues (23, 108).
Nitric Oxide, Sepsis and the Heart
Malcolm J. Lewis, Ajay M. Shah in Endothelial Modulation of Cardiac Function, 2020
NO produces a wide range of effects in different cells and tissues. NO interacts with targets via covalent (additive) and non-covalent (redox) reactions. Thus, both nitrosation of peptides and oxidation events that do not involve the attachment of the nitroso group are mechanisms of action of this versatile messenger. In biologic systems, NO readily reacts with oxygen (O2), superoxide (O2−), and transition metals, producing NOx, peroxynitrite (OONO), and metalo-NO adducts, respectively. These products can also produce nitrosative reactions at nucleophilic centers (Stamler, Singel and Loscalzo, 1992; Mohr, Stamler and Brune, 1994). The greater prevalence and reactivity of thiol groups explain the propensity for S-nitrosothiol (RS-NO) formation. Thus, metal- and thiol-containing proteins serve as major target sites for NO; these include signaling proteins, ion channels, receptors, enzymes and transcription factors (Table 5-3). An important heme-containing protein, soluble guanylate cyclase, undergoes a structural change upon NO binding. The enzyme becomes activated, producing cyclic guanosine monophosphate (cGMP), which mediates many of the target cell responses to NO, including vasorelaxation and inhibition of platelet aggregation.
The Role of Neuropeptides in the Normal and Pathophysiological Control of Blood Flow
Edwin E. Daniel in Neuropeptide Function in the Gastrointestinal Tract, 2019
The levels of CGRP present in the plasma of rats and humans are quite high, ranging between 9.7 and 71 pmol/1 in humans (mean 25 ± 1.2)32 and between 9 and 32 pmol/1 in rats.33 Studies involving young rats have suggested that the circulating levels of CGRP are largely derived from perivascular nerves.33 Such levels of CGRP, as mentioned previously, surpass the threshold level required to promote relaxation of human cerebral arteries pre-contracted with PGF2α.15 In humans and experimental animals, the systemic injection of CGRP produces hypotension and other alterations associated with hypotension (tachycardia, elevations in plasma NA and adrenaline) as well as increases in plasma levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP).28 In man, some effects, such as flushing (secondary to vasodilation), diastolic hypotension, tachycardia, and elevations in plasma catecholamines, have been observed at plasma CGRP levels of 56 pmol/1, well within the physiological levels present in humans.34,35 These results suggest that CGRP not only may act as a vascular neurotransmitter, but also may play a role as a neurohormone affecting vascular beds far distal to the sites of secretion.
Cyclic guanosine monophosphate and 10-year change in left ventricular mass: the Multi-Ethnic Study of Atherosclerosis (MESA)
Published in Biomarkers, 2021
Vinita Subramanya, Di Zhao, Pamela Ouyang, Wendy Ying, Dhananjay Vaidya, Chiadi E. Ndumele, Joao A. Lima, Eliseo Guallar, Ron C. Hoogeveen, Sanjiv J. Shah, Susan R. Heckbert, David A. Kass, Wendy S. Post, Erin D. Michos
Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for half of all HF cases and is more prevalent in older women (Sharma and Kass 2014). The pathophysiological processes implicated in HFpEF include arterial and left ventricular (LV) stiffness, systolic and diastolic dysfunction, systemic endothelial dysfunction, and renal sodium and fluid retention, culminating in an increase in LV filling pressures (Borlaug and Redfield 2011). Cyclic guanosine monophosphate (cGMP) is a second messenger that is intimately involved in these processes. It is synthesized by the activation of the soluble guanylate cyclase pathway that is nitric oxide (NO) dependent and through the particulate guanylate cyclase pathway that is regulated by natriuretic peptides (NP) (Tsai and Kass 2009, Greene et al.2013).
Signaling mechanisms of the platelet glycoprotein Ib-IX complex
Published in Platelets, 2022
Yaping Zhang, Samuel M Ehrlich, Cheng Zhu, Xiaoping Du
Both VWF and low-dose thrombin induce elevation of intracellular cGMP (cyclic guanosine monophosphate), which activates the cGMP-dependent protein kinase (PKG) [88]. cGMP plays biphasic role in platelet activation: low concentrations of cGMP generated in the early phase of platelet activation, via PKG, promote integrin activation and granule secretion mediated by GPIb-IX and other receptors [88,90]. High concentrations of cGMP and cGMP generated at later phases of thrombus formation inhibit platelet activation and limit the growth of platelet thrombi [88,91] via PKG and PKA-dependent signaling pathways [12]. The biphasic role of cGMP provides a potential explanation as to why GPIb-IX-mediated platelet activation is often seen as “measured” or “weak” and platelets adherent on the surface of a thrombus exposed to high shear appear less activated despite clear evidence of integrin activation.
The controlling role of nitric oxide within the shell of nucleus accumbens in the stress-induced metabolic disturbance
Published in Archives of Physiology and Biochemistry, 2021
Yasaman Husseini, Alireza Mohammadi, Gila Pirzad Jahromi, Gholamhossein Meftahi, Hedayat Sahraei, Boshra Hatef
Stress induces changes in gene expression of nNOS in regions related to stress responses and increases the production of NO (de Oliveira et al.2000, Krukoff and Khalili 1997). Nitric Oxide increases the production of cyclic guanosine monophosphate (cGMP) by the activation of the guanylate cyclase. This secondary messenger is also responsible for a part of the nitric oxide’s effects (Änggård 1994, Calabrese et al.2007). NO is a free radical which is able to affect a wide range of bio-molecules in the membrane, cytoplasm and intercellular space, due to its radical nature, and makes them undergo nitrosylation. It also as a neurotransmitter is a multifunctional messenger that can transfer the signal in antero- and retrograde directions (Feil and Kleppisch 2008). Moreover, nitric oxide can interact with dopaminergic and glutaminergic systems in several brain areas such as NAc and increases the release of them (Motahari et al.2016). On the other hand, the NAc is involved in the modulation of stress response (Ranjbaran et al.2017). Therefore, NO modulation in the NAc can affect the stress-related response of brain such as metabolic control shown in the current study. In the present study, although stress increased cortisol plasma concentrations, decreased the rat’s weight and changed the food and water intake, NO modulators affected these changes in different and dose-dependent manners.
Related Knowledge Centers
- Atrial Natriuretic Peptide
- Catalysis
- Cyclic Adenosine Monophosphate
- Cyclic Nucleotide
- Guanylate Cyclase
- Peptide Hormone
- Protein Kinase
- Second Messenger System
- Cell Membrane
- Guanosine Triphosphate