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Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Lipid mediators are synthesized and released by a wide variety of cell types, including neutrophilic, eosinophilic, and basophilic polymorphonuclear leukocytes, monocytes, mast cells, macrophages, and platelets. These lipid mediators can be grouped into two classes; (1) mediators derived from the arachidonic acid metabolism and (2) acetylated alkyl phosphoglycerides. These mediators and related compounds are now classified as autacoids rather than as mediators. Autacoids represent highly potent pharmacological agents previously described as autopharmacological agents or local hormones.
The Influence of Pituitary-Adrenal Axis on the Immune System
Published in Istvan Berczi, Pituitary Function and Immunity, 2019
In a recent textbook of endocrinology, Melmon395 discusses catecholamines, acetylcholine, serotonin, histamine, and vasoactive polypeptides under the general term autacoids, which is created from the Greek words autos meaning self, and akos meaning medical agent or remedy. The justification for this new classification is that these substances share common occurrences; often have coordinating interactions under physiologic or pathologic conditions; their direct effect often mimics or complements each other; and drugs that affect the synthesis or function of one often affect the body’s response to the others. Autacoids interact simultaneously at multiple levels in the body directly or indirectly and sometimes in combination. Their effects may be additive or antagonistic.
Control of blood vessels: intrinsic control
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
Autacoids (auto + akos, remedy) are organic, paracrine vasoactive chemicals; they are agents produced locally, released locally and acting locally on nearby vascular myocytes. Autacoids are involved mainly in pathological events, such as inflammation and bleeding. They include histamine, bradyki- nin, serotonin (5-hydroxytryptamine [5HT]), prostaglandins, thromboxane A2 (TXA2), leukotrienes and platelet-activating factor (PAF). The following ‘thumbnail sketches’ describe the principal autacoids.
Advances in the discovery of novel agents for the treatment of glaucoma
Published in Expert Opinion on Drug Discovery, 2021
Francesco Mincione, Alessio Nocentini, Claudiu T. Supuran
Among the many prostaglandins (PGs) known to date, PGD2, PGE2 and PGF2α are involved in ocular physiology [67]. Diverse PG receptors are expressed in various tissues including the eye, where they are involved in a host of physiological processes including chemotaxis, inflammation, immune response, etc [67]. PGD2 was demonstrated to decrease ocular aqueous flow in 1988 [68], but this autacoid is involved in immune responses and other essential processes, and it also provoked a strong reddening of the eye due to its pro-inflammatory action, and for such reasons, subsequent studies focused on PGF2, PGE2 and their agonists, which should not elicit immune responses and such strong adverse effects as PGD2 [67–70]. These autacoids exert their action through G-protein-coupled receptors (GPCR). There are four PGE2 receptors (EP1-EP4) and one PGF2α receptor (FP), which are widely expressed in various eye tissues, such as the cornea, conjunctiva, ciliary body, TM, iris and retina [69]. EP/FP receptor agonists constitute an interesting class of anti-glaucoma agents, as these compounds activate TM and ciliary muscle cells, increasing thus the aqueous outflow both by the non-conventional pathway [67,69,70]. Nowadays, at least four drugs belonging to the PG receptors agonists are in clinical use as anti-glaucoma agents: latanoprost 28 [71], bimatoprost 29 [72], travoprost 30 [73], and tafluprost 31 [74] (Figure 6).
Antiplatelet aggregation and endothelial protection of I4, a new synthetic anti-diabetes sulfonylurea compound
Published in Platelets, 2015
Lingman Ma, Na Lu, Guanzhong Wu
The endothelium plays a crucial role in the regulation of vascular tone and vessel wall homeostasis by releasing the autacoids prostacyclin (PGI) and NO [7]. Experimental evidence suggests that PGI2 prevents while TXA2 promotes the initiation and progression of atherogenesis through regulation of platelet activation and leukocyte-endothelial cell interaction [8]. Endothelial dysfunction in diabetic environment could be induced by hyperglycemia-induced overproduction of superoxide with consequent intracellular oxidative stress, NO and PGI2 reduction, endothelial nitric oxide synthase (eNOS) suppression [9] and advanced glycation end products (AGE) generation [10]. Research has confirmed that reduced NO production and decreased eNOs availability in the endothelium are major pathogenic mechanism in diabetic vascular complications in humans and experimental animals [11]. Furthermore, high glucose not only arrests the proliferative response of endothelium cells but also leads to their activation associated with increased expression of adhesion molecules such as ICAM-1 and vascular cellular adhesion molecule-1 (VCAM-1). This effect may become more significant with increasing exposure to a high concentration of glucose [12].
Phage display technology for target determination of small-molecule therapeutics: an update
Published in Expert Opinion on Drug Discovery, 2020
Yoichi Takakusagi, Kaori Takakusagi, Kengo Sakaguchi, Fumio Sugawara
To improve next-generation drug R&D methods, there are some key points to be considered. Drug behavior in vivo (pharmacodynamics) should be considered during drug screening. This enables the early identification of modulators for specific physiological conditions, such as blood perfusion and oxygen dependence (e.g., hypoxia in tumors) that are responsible for malignant transformation or therapeutic resistance. In many cases, conventional drug screening has been conducted using a static endpoint method, such as the inhibition of the enzyme activity, signal transduction, cell proliferation, or cytotoxicity. This approach often results in the drug’s failure in the preclinical or clinical phase, due to drug inactivation effects, insufficient blood concentration, and the presence of adverse effects in patients. Alternatively, some compounds, such as hormones or autacoids, may provide a medical benefit only when tested in the living body. Indeed, SQAP, a semi-synthetic derivative of a natural product isolated from sea algae, enhanced the radiosensitivity of tumors only in vivo [47]. Experiments using inducible pluripotent stem cells (iPSCs) and immune checkpoint inhibitors showed that the drug developed by testing their effect on reprogramming and immunomodulation resulted in a better prognosis than the agents developed with conventional testing (selective enzyme inhibition or cell killing). Moreover, the identification of drugs targeting proteins involved in cell metabolism could normalize cells, vessels, and tissues affected in inflammatory and other pathological states. The use of PD technology in vivo might be a strategy to investigate pharmacodynamics and contribute to the development of new drugs.