Possible role of insulin-like growth factor-II C-peptide on catecholamine release and ultrastructural aspects of chromaffin cells in the adrenal gland of the frog

The present study was undertaken to demonstrate that insulin-like growth factor-II C-peptide (IGF-II C-peptide) affects the function of the adrenal gland of Rana ridibunda (Anura, Amphibia) by stimulating chromaffin cells. Previous studies have shown that insulin-like growth factors affect adrenal gland function in mammals. On the basis of these findings, frogs were injected with IGF-II C-peptide (2.5 microg/0.2 ml), whereas control animals were injected with Ringer solution (0.2 ml). The adrenal glands were removed at 12 and 48 h after injection and fixed, embedded in paraffin wax and Epon, and examined by immunohistochemistry and transmission electron microscopy to investigate whether there were structural changes and activation of chromaffin cells in the frog adrenal gland. Sections were stained with hematoxylin and eosin for overall tissue analysis and, in parallel, serotonin was localized using the streptavidin-biotin complex technique while dopamine beta-hydroxylase was shown by the peroxidase-antiperoxidase-3, 3'-diaminobenzidine tetrachloride method. After injection of IGF-II C-peptide, chromaffin cells released serotonin and synthesized dopamine beta-hydroxylase. The most pronounced effect of IGF-II C-peptide on the chromaffin cells was observed at 12h after injection. Our results indicate that there is a possible role of IGF-II C-peptide on chromaffin cell activity enhancing catecholamine release in the adrenal gland of the frog.     

Serotonin dynamics in and around the central nervous system: Is autism solvable without fundamental insights?

Altered serotonin (5-hydroxytryptamine, 5-HT) signaling has been implicated in some developmental abnormalities of autism spectrum disorder (ASD). However, the presumed role of 5-HT in ASD raises new questions in fundamental neuroscience. Specifically, it is not clear if the current piecemeal approach to 5-HT signaling in the mammalian body is effective and whether new conceptual approaches may be required. This review briefly discusses 5-HT production and circulation in the central nervous system and outside of it, especially with regard to ASD, and proposes a more encompassing approach that questions the utility of the “neurotransmitter” concept. It then introduces the idea of a generalized 5-HT packet that may offer insights into possible links between serotonergic varicosities and blood platelets. These approaches have theoretical significance, but they are also well positioned to advance our understanding of some long-standing problems in autism research.     

Enterochromaffin and serotonin cells are abnormal for patients with colonic inertia

PURPOSE: In recent studies, serotonin and several gut peptides have been shown to serve as regulators of colonic transit. Thus, the distribution, density, and intensity of cells secreting serotonin or certain gut peptides could be abnormal in patients with colonic inertia. The aim of this study was to evaluate the distribution, density, and staining intensity of enterochromaffin and serotonin cells in the colonic mucosa of patients with colonic inertia compared with a control group. METHODS: Between 1993 and 1998 tissue blocks from the right and left side of the colon were obtained in 19 consecutive patients (18 females; mean age, 43.7±11.5 years) who underwent subtotal colectomy for colonic inertia. The control group consisted of colonoscopic biopsies from the right and left colon of 15 patients (all females; mean age, 52.7±16.5 years) for indications other then constipation, inflammatory bowel diseases, or carcinoma. Immunocytochemical staining of enterochromaffin and serotonin cells were performed on 4 µm tissue sections with the primary rabbit antibody against chromogranin A or serotonin, and the biotinylated secondary antibody and enzyme-labeled-streptavidin. The average cell number per microscopic field (×200) was calculated and the proportion of cells with various staining distribution was expressed as the percentage of the entire positive cell population as low, moderate, and high intensity. Student'st-test and chi-squared test were used for statistical analysis, with significance level set atP<0.05. RESULTS: The quantity of both enterochromaffin cells (16.8±10.2) and serotonin cells (12.1±6.4) in the mucosa of the left colon in patients with colonic inertia was significantly higher when compared with the right side of the colon (enterochromaffin cells, 9.4±6.0; serotonin cells, 7.8±3.6;P<0.01). The percentage of both types of cells with low staining intensity was increased, whereas the cells with high and moderate staining intensity were decreased (P<0.01) in the left colon as compared with the right. The number of enterochromaffin cells in left-sided colonic mucosa was significantly higher in the colonic inertia group than in the control group (16.8±10.1vs. 10.4±6.0;P<0.05). Moreover, the numbers of serotonin cells in both the right and left colon was also significantly higher in the colonic inertia group than in the control group (right, 7.8±3.6vs. 4.1±2.4; left, 12.1±6.4vs. 5.8±3.7;P<0.01). In both sides of the colon, the percentage of enterochromaffin and serotonin cells with low staining was significantly higher, whereas percentage of those cells with high or moderate staining was significantly lower in the colonic inertia group than in the control group. In the colonic inertia group there was a significantly positive correlation between numbers of enterochromaffin and serotonin cells (right side,P<0.01; left side,P<0.05). CONCLUSION: In patients with colonic inertia, the number of both enterochromaffin and serotonin cells are significantly increased in the colonic mucosa, especially in the left colon. As indicated by staining distribution, enterochromaffin and serotonin cells contain significantly less hormone than do the same cells in the control group.Funded in part by a grant from the Eleanor Naylor Dana Charitable Trust.Read at The American Society of Colon and Rectal Surgeons' 100th Anniversary and Tripartite Meeting, Washington, D.C., May 1 to 6, 1999.     

Primary dysfunction in aggregation and secretion of SHRSP platelets: Not secondary to the circulation of “exhausted” platelets

Summary The thrombin-induced secretion of [¹⁴C]-serotonin and adenine nucleotides from stroke-prone spontaneously hypertensive rats (SHRSP) platelets was markedly reduced with the development of hypertension accompanying hypoaggregability compared with that from age-matched Wistar Kyoto rats (WKY) platelets. Calcium Ionophore A 23187-induced secretion and aggregation were also attenuated in SHRSP platelets. Additionally, an enhancement of platelet secretion as well as aggregation by extracellular Ca²⁺ was less in SHRSP platelets than in WKY platelets. The platelet contents of adenine nucleotides and serotonin were not different between SHRSP and WKY at 5–16 weeks of age whereas they became significantly lower in SHRSP beginning at 22 weeks. The serotonin content in SHRSP platelets at 36 weeks of age was only 55% of that in WKY platelets. It is suggested that the reduced platelet aggregation and secretion observed in SHRSP platelets at ages lower than approximately 20 weeks are not secondary phenomena to the circulation of degranulated platelets, but the primary defect of SHRSP platelets appears to be an impaired function of Ca²⁺.     

Binding-Induced Fluorescence of Serotonin Transporter Ligands: A Spectroscopic and Structural Study of 4-(4-(Dimethylamino)phenyl)-1-methylpyridinium (APP+) and APP+ Analogues

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Inhibition of the liver expression of arylalkylamine N-acetyltransferase increases the expression of angiogenic factors in cholangiocytes

Background and aims

Reduction of biliary serotonin N-acetyltransferase (AANAT) expression and melatonin administration/secretion in cholangiocytes increases biliary proliferation and the expression of SR, CFTR and Cl^–/HCO₃^– AE2. The balance between biliary proliferation/damage is regulated by several autocrine neuroendocrine factors including vascular endothelial growth factor-A/C (VEGF-A/C). VEGFs are secreted by several epithelia, where they modulate cell growth by autocrine and paracrine mechanisms. No data exists regarding the effect of AANAT modulation on the expressions of VEGFs by cholangiocytes.

Methods

In this study, we evaluated the effect of local modulation of biliary AANAT expression on the cholangiocytes synthesis of VEGF-A/C.

Results

The decrease in AANAT expression and subsequent lower melatonin secretion by cholangiocytes was associated with increased expression of VEGF-A/C. Overexpression of AANAT in cholangiocyte lines decreased the expression of VEGF-A/C.

Conclusions

Modulation of melatonin synthesis may affect the expression of VEGF-A/C by cholangiocytes and may modulate the hepatic microvascularization through the regulation of VEGF-A/C expression regulating biliary functions.     

Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder

Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRIs), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of amygdala activation by negative facial expressions in MDD patients. We treated fifteen MDD patients (22–55 years) with paroxetine 20–50 mg/day. After 6 and 12 weeks, we quantified (1) clinical response (≥50% decrease in Hamilton Depression Rating Scale (HDRS), (2) SERT occupancy in both amygdala measured by repeated [¹²³I]β-CIT single photon emission computed tomography (SPECT), and (3) amygdala activation when viewing fearful and angry (negative) faces with repeated functional MRI scans. Response rates were 4/15 and 9/15 at 6 and 12 weeks, respectively. Attenuation of left amygdala activation was associated with amygdala SERT occupancy (P=0.006) and response (P=0.015). This association may provide a rationale for decreased limbic activity seen during treatment of MDD. It might also explain the rapid decrease in negative attentional bias and amygdala activation caused by SSRIs.     

Serotonin syndrome in patients with peripheral neuropathy: a diagnostic challenge

According to the Hunter Serotonin Toxicity Criteria, the presence of either clonus or hyperreflexia is a must for making a diagnosis of serotonin syndrome (SS). We report five patients with SS who had areflexia because of associated polyneuropathy. None of the patients fulfilled the Hunter criteria for SS. However, all five patients had features suggestive of neuromuscular hyperactivity, autonomic hyperactivity and altered mental status and fulfilled the Sternbach criteria for SS. All patients responded to cyproheptadine within 5 days to 2 weeks duration. These cases highlight the limitations of the Hunter criteria for SS in patients with associated polyneuropathy.     

Dependence Potential of Tramadol: Behavioral Pharmacology in Rodents

Tramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.