Despite functional studies demonstrating the role of HT in u

Despite functional studies demonstrating the role of 5-HT in ureteral contractility, the source of endogenous 5-HT in the ureter is unclear. Since 5-HT-containing enterochromaffin cells, which are present in the gastrointestinal tract, could not be found in the ureter (Nocito et al., 2007, Ripoche, 2011, Theoharides et al., 1982), it appears that platelets and mast Phosphatase Inhibitor Cocktail 3 (100X in DMSO) might be the source of 5-HT in this tissue. Particularly where intra-ureteral pressure may increase due to the presence of calculi, it is possible that increased vascular permeability secondary to inflammation could result in the release of 5-HT from platelets in the tissues. Alternatively, mast cells playing a major role in the inflammatory process have been observed in all layers of the porcine ureteral wall under normal conditions (Jerde et al., 2000, Vodenicharov et al., 2005). Mast cells present in the ureter are most likely involved in maintaining local homeostasis and also play an important role in the regulation of ureteral motility via the release of mediators including histamine and 5-HT in inflammatory circumstances. While our preliminary data failed to find any ureteral response to histamine, it is possible that mast cell regulatory mechanisms occur via 5-HT. Furthermore, an upregulation of 5-HT2A receptors may occur during obstruction and in the rabbit ureter it has been shown that 5-HT-stimulated contractile responses are enhanced in the presence of ureteral obstruction (Yalcin et al., 2013).
Conclusion The present data indicate that 5-HT enhances the overall phasic contractile activity of the porcine ureter by increasing both the frequency and magnitude of contractions. With increasing age, the overall contractile activity to 5-HT is depressed, although with no change in the frequency responses to 5-HT. The predominant receptor mediating both frequency and contractile responses to 5-HT is the 5-HT2A receptor subtype and this does not appear to change with increasing age.
Acknowledgements Iris Lim received a Bond University Higher Degree Research Scholarship.
Introduction Depression is a major human blight worldwide. According to the WHO, about 350 million people suffer from depression (Smith, 2014). The main problem is that most of the patients with depression do not receive evidence-based interventions resulting in a huge treatment gap (Shidhaye et al., 2017). Moreover, due to addiction, tolerability problems and multiple side effects, 40%–60% of patients with major depressive disorder do not respond adequately to first-line pharmacotherapies (Thase et al., 2017). Serotonin (5-HT) is a monoamine neurotransmitter that plays an important role in physiological functions, such as sleep, feeding, sexual behavior, temperature regulation, pain, and cognition, as well as in pathological states including mood disorders, anxiety disorders, psychosis, and pain disorders (Chilmonczyk et al., 2015). It is believed that the 5-HT system has been implicated in the pathogenesis of depressive disorder (Blier and El, 2013). According to the relevant research, the 5-HT system plays an important role in both the pathophysiology and treatment of depression (Mouri et al., 2016). The 5-HT hypothesis in depression has been widely accepted. Therefore, selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressants used to treat depression (Gentile, 2015). However, the latest study found that SSRIs have become a class of drugs that can produce troublesome side effects, like sexual dysfunction, gastrointestinal reactions, anxiety symptoms, palpitations, drowsiness, etc. (Riediger et al., 2017) Persistent alterations in neurotransmitter-mediated synaptic transmission could produce the development of a persistent depressive affective state. Moreover, long-term synaptic plasticity has been a major target of study in cognition, memory storage, and depression (Vose and Stanton, 2017). It is reported that depressive subjects have neurocognitive impairment in attention, memory, learning ability and executive function (Gualtieri et al., 2006; Porter et al., 2003). Some animal studies have reported that depressed rats had spatial learning deficits and impaired reference memory (Bhagya et al., 2008). Others observed that long-term potentiation (LTP) induction was impaired in depressed rats (Mahati et al., 2016).