Comparative studies of somatostatin-14 and some of its fragments on passive avoidance behavior, open field activity and on barrel rotation phenomenon in rats

Vécsei, László; Pávó, Imre; Zsigo, Jozsef; Penke, Botond; Widerlöv, Erik

doi:10.1016/0196-9781(89)90007-7

Cited by 22 publications

(8 citation statements)

References 23 publications

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“…antinociceptive effects (Chapman and Dickenson, 1992;Helyes et al, 2004;Pinter et al, 2006;Sandor et al, 2006) also induced barrel rotations (Van Wimersma Greidanus et al, 1987;Vécsei et al, 1989). This would fit well into our observations if not for the fact that SP inhibited the release and activity of SOM (McIntosh et al, 1987).…”

Section: Accepted Manuscriptsupporting

confidence: 88%

Biological evaluation and molecular docking studies of AA3052, a compound containing a μ-selective opioid peptide agonist DALDA and d-Phe-Phe-d-Phe-Leu-Leu-NH2, a substance P analogue

Kowalczyk

Kleczkowska

Rękawek

et al. 2016

European Journal of Pharmaceutical Sciences

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The design of novel drugs for pain relief with improved analgesic properties and diminished side effect induction profile still remains a challenging pursuit. Tolerance is one of the most burdensome phenomena that may hamper ongoing opioid therapy, especially in chronic pain patients. Therefore, a promising strategy of hybridizing two pharmacophores that target distinct binding sites involved in pain modulation and transmission was established. Previous studies have led to the development of opioid agonist/NK1 agonist hybrids that produce sufficient analgesia and also suppress opioid-induced tolerance development. In our present investigation we assessed the antinociceptive potency of a new AA3052 chimera comprised of a potent MOR selective dermorphin derivative (DALDA) and an NK1 agonist, a stabilized substance P analogue. We have shown that AA3052 significantly prolonged responses to both mechanical and noxious thermal stimuli in rats after intracerebroventricular administration. Additionally, AA3052 did not trigger the development of tolerance in a 6-day daily injection paradigm nor did it produce any sedative effects, as assessed in the rotarod performance test. However, the antinociceptive effect of AA3052 was independent of opioid receptor stimulation by the DALDA pharmacophore as shown in the agonist-stimulated G-protein assay. Altogether the current results confirm the antinociceptive effectiveness of a novel opioid/SP hybrid agonist, AA3052, and more importantly its ability to inhibit the development of tolerance.

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Section: Accepted Manuscriptsupporting

confidence: 88%

Biological evaluation and molecular docking studies of AA3052, a compound containing a μ-selective opioid peptide agonist DALDA and d-Phe-Phe-d-Phe-Leu-Leu-NH2, a substance P analogue

Kowalczyk

Kleczkowska

Rękawek

et al. 2016

European Journal of Pharmaceutical Sciences

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“…SST ‫מ/מ‬ mice, e.g., were remarkably impaired in a motor learning task (Zeyda et al 2001), and previous publications have raised the issue that some observed effects of somatostatin on memory formation might at least partly be due to an affected motor performance. Most of the above-mentioned studies, however, employed a passive avoidance-learning paradigm (Haroutunian et al 1987;DeNoble et al 1989;Vecsei et al 1989), which does not allow for a discrimination of the impact of somatostatinergic processes onto locomotor behavior from the peptide's role in memory processes. In contrast, the comparative analysis of cued and contextual fear memory formation employed in the present work allowed us to rule out a significant motor impairment in SST ‫מ/מ‬ mice.…”

Section: Discussionmentioning

confidence: 99%

Role of the somatostatin system in contextual fear memory and hippocampal synaptic plasticity

Kluge¹,

Stoppel²,

Szinyei³

et al. 2008

Learn. Mem.

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Somatostatin has been implicated in various cognitive and emotional functions, but its precise role is still poorly understood. Here, we have made use of mice with somatostatin deficiency, based upon genetic invalidation or pharmacologically induced depletion, and Pavlovian fear conditioning in order to address the contribution of the somatostatin system to associative fear memory. The results demonstrate an impairment of foreground and background contextual but not tone fear conditioning in mice with targeted ablation of the somatostatin gene. These deficits were associated with a decrease in long-term potentiation in the CA1 area of the hippocampus. Both the behavioral and the electrophysiological phenotypes were mimicked in wild-type mice through application of the somatostatin-depleting substance cysteamine prior to fear training, whereas no further deficits were observed upon application in the somatostatin null mutants. These results suggest that the somatostatin system plays a critical role in the acquisition of contextual fear memory, but not tone fear learning, and further highlights the role of hippocampal synaptic plasticity for information processing concerning contextual information.

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“…In contrast to lower doses, icv administration of SST at relatively higher doses elicits anorexigenic effect in rats and mice [190][191][192][193][194]. The occurrence of dose associated opposing effects of SST was argued due to the impact of competitive behavioural changes or leakage of SST into peripheral circulation where SST is known to exert an inhibitory role [195][196][197]. Furthermore, enhanced food intake in response to icv injection of SST in rodents leads to activation of SST signaling in the brain.…”

Section: Effect Of Somatostatin and Its Analogues On Satietymentioning

confidence: 99%

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

Kumar

Singh

2020

IJMS

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Obesity is one of the major social and health problems globally and often associated with various other pathological conditions. In addition to unregulated eating behaviour, circulating peptide-mediated hormonal secretion and signaling pathways play a critical role in food intake induced obesity. Amongst the many peptides involved in the regulation of food-seeking behaviour, somatostatin (SST) is the one which plays a determinant role in the complex process of appetite. SST is involved in the regulation of release and secretion of other peptides, neuronal integrity, and hormonal regulation. Based on past and recent studies, SST might serve as a bridge between central and peripheral tissues with a significant impact on obesity-associated with food intake behaviour and energy expenditure. Here, we present a comprehensive review describing the role of SST in the modulation of multiple central and peripheral signaling molecules. In addition, we highlight recent progress and contribution of SST and its receptors in food-seeking behaviour, obesity (orexigenic), and satiety (anorexigenic) associated pathways and mechanism.Contrary to obesity, satiety is a sense of fullness due to ephemeral lack of interest in further ingestion of food, which eventually leads to the suppression of appetite. Fullness is supposed to have a vital role in weight management because it will impact the frequency and amount of food and drink consumed later [53]. The feeling of satiety is a well-organized and biologically oriented process [54,55]. Satiety is a well-articulated process which reduces gastric distension and cholecystokinin (CCK) release in gut post ingestion of nutrients and importantly has been associated with signals from periphery via vagal afferent fibers that terminate in nucleus of the tractus solitaries (NTS) in the brain stem [56]. Besides, leptin, a hormone secreted by adipocytes, is also associated with satiety signals and studies further indicate that satiety response to CCK that was blocked in leptin receptor-deficient rat was regained following restoration of the leptin receptor in arcuate nucleus (ARC) [57][58][59]. Studies also support the role of NTS vagus afferent in response to leptin [60,61]. Feeling satiated will, in the long run, smother the inclination for cravings and lead to lesser consumption of food in the next meal. Satiety is not a response; it involves a complex mechanism for its operation, which includes the crucial role of the hypothalamus and peripheral hormones and determines energy expenditure [62]. Measurement of satiation can be done either directly by assessing food intake or indirectly by subjectively rating the urge for appetite [63]. Schwartz et al. demonstrated that hypothalamus is the central brain region responsible for adiposity signal; however, it is not an active participant in satiety [64]. It is interesting to note that most satiety associated information is relayed to NTS afferent fibers from the vagus nerve and afferent from GIT through the spinal cord. Mechanical or chemical stimula...

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Comparative studies of somatostatin-14 and some of its fragments on passive avoidance behavior, open field activity and on barrel rotation phenomenon in rats

Cited by 22 publications

References 23 publications

Biological evaluation and molecular docking studies of AA3052, a compound containing a μ-selective opioid peptide agonist DALDA and d-Phe-Phe-d-Phe-Leu-Leu-NH2, a substance P analogue

Biological evaluation and molecular docking studies of AA3052, a compound containing a μ-selective opioid peptide agonist DALDA and d-Phe-Phe-d-Phe-Leu-Leu-NH2, a substance P analogue

Role of the somatostatin system in contextual fear memory and hippocampal synaptic plasticity

Role of Somatostatin in the Regulation of Central and Peripheral Factors of Satiety and Obesity

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