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Physiological and Pathophysiological Roles of VIP, Somatostatin, Opioids, Galanin, GRP, and Secretin
Published in Edwin E. Daniel, Neuropeptide Function in the Gastrointestinal Tract, 2019
Jan D. Huizinga, Julio Pintin-Quezada
As many as 18 bioactive peptides have been found to belong to the opioid peptide family, which share the COOH-terminal part of enkephalin.86 The receptors involved in control of gastrointestinal function are μ-, μ1-, δ-, and κ-receptors.87,88 μ-Receptors have the chemicals morphine and morphoceptin as agonists. Enkephalins appear to be recognized by δ-receptors as well as μ-receptors, but d-pen2, D-pen5-enkephalin is highly selective for δ-receptors. κ- Receptors selectively recognize the endogenous prodynorphin products.89–91 See Chapter 11 for more details about selective opioid agonists and other general aspects of the opioids.
Tropical Colorectal Surgery
Published in Peter Sagar, Andrew G. Hill, Charles H. Knowles, Stefan Post, Willem A. Bemelman, Patricia L. Roberts, Susan Galandiuk, John R.T. Monson, Michael R.B. Keighley, Norman S. Williams, Keighley & Williams’ Surgery of the Anus, Rectum and Colon, 2019
Meheshinder Singh, Kemal I. Deen
In situations wherein actinomycotic sulphur granules are identified and a preoperative diagnosis is made following a percutaneous aspiration, high-dose antibiotics can be therapeutic precluding the need for surgery. High-dose penicillin is the preferred choice of treatment (IV Penicillin G at a dose of 10–20 million units/day divided in 4 to 6 hours followed by oral Pen 2–4 g/day or amoxicillin for 6–12 months).
CNS Receptors for Opioids
Published in Edythe D. London, Imaging Drug Action in the Brain, 2017
Richard J. Knopp, Mary Hunt, James K. Wamsley, Henry I. Yamamura
CTP (Pelton et al., 1985) is a highly selective μ opioid receptor antagonist in vitro. The pA2 values measured for CTP antagonism of the selective μ opioid agonist PL-17 in the MVD, which contains a small population of μ opioid receptors (Leslie, 1987), and in the GPI are not significantly different (Shook et al., 1987a). CTP does not antagonize the response of the MVD to the selective δ agonist [D-Pen2, D-Pen5]enkephalin (DPDPE). The in vivo activity of CTP is more complex, however. CTP competitively antagonizes the analgesic and gastrointestinal antitransit response produced by PL-17 at spinal and supraspinal levels, but also appears to noncompetitively (Schild slope < 1) block intracerebroventricular (i.c.v.) and intrathecal (i.t.) analgesic response to DPDPE (Shook et al., 1987b). It is unlikely that CTP is acting on δ opioid receptors, for which it has very low affinity (Pelton et al., 1985), since CTP does not block the antitransit response elicited by i.t. DPDPE (Shook et al., 1987b). The inhibition of the DPDPE analgesic effect could be related to the potentiating effect of δ opioid agonists on μ opioid receptor-mediated analgesia described by Vaught and Takemori (1979). This effect is interpreted by some investigators as a result of the presence of a μ-δ opioid receptor complex (see δ opioid receptor subtypes below). DPDPE given i.c.v. at subanalgesic doses is able to potentiate morphine-induced analgesia (Heyman and Porreca, 1989; Jiang et al., 1990). If DPDPE were acting to potentiate the analgesic activity of endogenous enkephalins at μ opioid receptors in the Shook et al. (1987b) study, then it is likely that CTP would be able to antagonize the enhanced enkephalin response. This effect would explain the low slope value produced by the Schild analysis and is consistent with the modulatory relationship between the “morphine” and “enkephalin” receptors hypothesized by Vaught et al. (1982). Thus, it is reasonable to conclude that CTP is a selective μ opioid receptor antagonist in vivo as well as in vitro, despite the unexpected result with DPDPE.
Neuroprotective effect of quercetin through targeting key genes involved in aluminum chloride induced Alzheimer’s disease in rats
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Hala A Elreedy, Asmaa M. Elfiky, Asmaa Ahmed Mahmoud, Khadiga S. Ibrahim, Mohamed A Ghazy
Gamma-secretase is an intramembrane aspartyl protease which engaged in Alzheimer’s disease through the proteolysis of APP. Thus, gamma-secretase creates the pathogenic Aβ 1–42 peptide that causes amyloid plaques [43,44]. A protein called Presenilin I (PSEN1) belongs to the aspartic protease family and is involved in the control of intramembrane proteolysis [8]. PSEN1 was believed to be a central, catalytic moiety of the gamma-secretase complex. PSEN1 was reported to be capable of cleaving substrates in the absence of Nicastrin (NCT), APH1 and presenilin enhancer-2 (PEN-2) in an activity assay performed in the liposomes [45]. Therefore, PSEN1 is a candidate target gene in drug design against AD. In the current research, we evaluated the levels of PSEN1 and APH1, two different components of gamma-secretase, in the hippocampus of rat brains. Both PSEN1 and APH1 levels were elevated in the AlCl3-induced AD group in comparison with the normal group. Meanwhile, PSEN1 gene expression level was significantly decreased in co-administration of AlCl3 with Q 50 mg kg-1 to AlCl3-induced AD rat. Suggesting that polyphenols could act as an inhibitor of PSEN1, a study by Lakey-Beitia and Berrocal [46] intended that polyphenols could occupy the active site of gamma-secretase (displacing the water molecule needed for catalysis by the enzyme), would inactivate the enzyme and decrease Aβ formation. On the other hand, Q at 50 mg kg-1 to AlCl3 -induced AD rats showed no significant effect on APH1gene expression compared to AlCl3 group.
The brain heme oxygenase/biliverdin reductase system as a target in drug research and development
Published in Expert Opinion on Therapeutic Targets, 2022
Heme oxygenase-1 is also a target for opioid drugs. In a diabetic mice model induced by the injection of streptozotocin, the administration of the HO-1 inducer Co-PP-IX (10 mg/kg intraperitoneally for 5 days) fully counteracted the mechanical and thermal hypersensitivity caused by diabetes [123]. These beneficial effects correlated with the overexpression of HO-1 in spinal cord, dorsal root ganglia and sciatic nerve samples [123]. Interestingly, in this preclinical model of diabetes mellitus, Co-PP-IX potentiated the mechanical antiallodynic, thermal antihyperalgesic and thermal antiallodynic effects produced by low-dose morphine (0.5 mg/kg) [123]. The active involvement of HO-1 on these morphine-induced antinociceptive effects were confirmed by the evidence that the administration of the HO inhibitor Sn-PP-IX (10 mg/kg intraperitoneally) cured them [123]. Finally, Co-PP-IX strengthened the antinociceptive effects of morphine by increasing the expression of opioid µ receptor in the spinal cord [123]. In the streptozotocin-treated mice, Co-PP-IX potentiated the antinociceptive effects of the δ opioid receptor agonist [d-Pen(2), d-Pen(5)]-Enkephalin with a mechanism involving the HO-1-induced generation of CO [124]. In an inflammatory pain model, such as the carrageenan model, HO-1-derived CO has been shown to produce antinociceptive effects through the activation of ATP-sensitive K+ channels [125].
Memorcise and Alzheimer’s disease
Published in The Physician and Sportsmedicine, 2018
Paul D. Loprinzi, Emily Frith, Pamela Ponce
The initial step in the production of Aβ is cleaving the large APP by beta- and gamma-secretase proteases [30]. The primary β-secretase enzyme is β-site APP cleaving enzyme (BACE1). Deletion of BACE1 reduces Aβ levels and may help to prevent memory decline [31]. Gamma-secretase also plays a critical role in the generation of Aβ by interacting with four core proteins, namely presenilin, nicastrin, aph-1, and pen-2 [32], which elevate levels of Aβ. Increases in Aβ exacerbate disrupted cholesterol homeostasis via Aβ’s direct binding affinity for lipid bilayers, altering membrane fluidity [33] and perturbing ion channel function and Ca2+ homeostasis [34]. As noted above, traditionally, extracellular Aβ has been implicated in the pathophysiology of AD. More recent discussions implicate intraneuronal Aβ accumulation also contributing to the synapse pathology of AD, particularly via altered morphology of neurites and synapses [35,36]. These proteins exhibit prion-like properties [37,38], with the intracellular transfer of misfolded proteins inducing an aggregated state [39].