From Selye’s and Szabo’s Cysteamine-Duodenal Ulcer in Rats to Dopamine in the Stomach: Therapy Significance and Possibilities

Abstract

We reviewed gastric ulcer healing by dopamine considering several distinctive duodenal key points. Selye and Szabo describe the cysteamine-induced duodenal ulcer in rats as a duodenal stress ulcer in patients. Szabo’s cysteamine duodenal ulcer as the dopamine duodenal healing and cysteamine as a dopamine antagonist signifies the dopamine agonists anti-ulcer effect and dopamine antagonists ulcerogenic effect. From these viewpoints, we focused on dopamine and gastric ulcer healing. We mentioned antecedent studies on the dopamine presence in the stomach and gastric juice. Then we reviewed, in the timeline, therapy significance arising from the anti-ulcer potency of the various dopamine agonists, which is highly prevailing over the quite persistent beneficial evidence arising from the various dopamine antagonists. Meanwhile, the beneficial effects of several peptides (i.e., amylin, cholecystokinin, leptin, and stable gastric pentadecapeptide BPC 157, suggested as an acting mediator of the dopamine brain-gut axis) were included in the dopamine gastric ulcer story. We attempt to resolve dopamine agonists/antagonists issue with the dopamine significance in the stress (cysteamine as a prototype of the duodenal stress ulcer), and cytoprotection (cysteamine in small dose as a prototype of the cytoprotective agents; cysteamine duodenal ulcer in gastrectomized rats). Thereby, along with dopamine agonists’ beneficial effects, in special circumstances, dopamine antagonists having their own ulcerogenic effect may act as “mild stress (or)” or “small irritant” counteracting subsequent strong alcohol or stress procedure-induced severe lesions in this particular tissue. Finally, in the conclusion, as a new improvement in further therapy, we emphasized the advantages of the dopamine agents’ application in lower gastrointestinal tract therapy.

Cysteamine HCl Administration Impedes Motor and Olfactory Functions, Accompanied by a Reduced Number of Dopaminergic Neurons, in Experimental Mice: A Preclinical Mimetic Relevant to Parkinson’s Disease

“…Considering that anxiety is the pathogenic overlap of PD, this linkage highlights the intricate interplay between the GI disorder and the pathogenesis of PD [39]. Cys-HCl administration has been reported to impair dopamine synthesis in the GI tract, resulting in gastric ulceration leading to affective and neurodegenerative disorders [7]. The degeneration of dopamine-producing neurons in the SN and OB is a prominent neuropathogenic hallmark of PD [40,41].…”

“…As the aberrant circadian rhythm often coincides with GI disorders, the Cys-HCl-induced pathophysiology of the GI tract can result in sleep disorders leading to mood, neurocognitive, and neurological disorders [5,6]. Moreover, ulceration in the GI tract caused by Cys-HCl can also deteriorate the gut-brain axis, contributing to behavioral and neurophysiological abnormalities [7,8]. As Cys-HCl can cross the blood-brain barrier (BBB), it has become more apparent that it can also cause anxiety and neurocognitive impairments [9].…”

“…As Cys-HCl can cross the blood-brain barrier (BBB), it has become more apparent that it can also cause anxiety and neurocognitive impairments [9]. Furthermore, few animal studies have shown that Cys-HCl treatment can induce neurotoxicological effects similar to those provoked by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an authenticated neurotoxin known to induce the clinical symptoms of Parkinson's disease (PD) [7,10]. Cys-HCl competitively antagonizes various ion channels and neurotransmitter systems due to its structural resemblance to ethylamine, a precursor of norepinephrine, dopamine, and serotonin, which serve as crucial neuromodulators of the stress response, motor function, mood, and cognitive functions [10,11].…”

“…Cys-HCl competitively antagonizes various ion channels and neurotransmitter systems due to its structural resemblance to ethylamine, a precursor of norepinephrine, dopamine, and serotonin, which serve as crucial neuromodulators of the stress response, motor function, mood, and cognitive functions [10,11]. In particular, Cys-HCl-mediated GI dysfunction in association with the alteration of the dopamine system has been an intense research focus [7]. Meanwhile, the deleterious effects of Cys-HCl on neuroplasticity responsible for movement disorders have also been recognized, but to a lesser extent [12].…”