Ultrasonic vocalization in response to unavoidable aversive stimuli in rats: effects of benzodiazepines

The effects of two benzodiazepine derivatives (diazepam, 0.5-1 mg/kg; alprazolam, 1.25-2.5 mg/kg) on ultrasonic calling elicited in adult rats by unavoidable aversive stimuli (footshocks) were investigated. The results show that either diazepam or alprazolam affected the duration of ultrasonic calls. In particular, a significant decrease in the length of ultrasounds was found in the group of animals treated with these benzodiazepines. The effects of diazepam were counteracted by the benzodiazepine-antagonist Ro 15-1788. On the other hand, neither a neuroleptic agent, such as haloperidol (0.5-1 mg/kg), nor an antidepressant, such as desipramine (5-10 mg/kg) influenced the parameters of ultrasonic emission in this experimental situation. The present results suggest that ultrasonic vocalization in response to unavoidable aversive stimuli could be considered as a potential new tool for studying drugs with antianxiety properties

Myogenic effect of SP-1f and SP-1h two novel 3-adrenoceptor (3-AR) agonists in human colonic circular smooth muscle

The effect of two novel 3-adrenoceptor (3-AR) agonists SP-1f and SP-1h on human colon circular smooth muscle contractility and 3-AR mRNA expression have been determined. 3-AR is ascertained co-participates to the control of the gut motility. Isometric tension on human colon muscle strips was measured in response to increasing concentrations of SP-1f, SP-1h and (-)-isoprenaline, alone and in the presence of Betaxolol, ICI 11,855 and SR 59230A (1-, 2- and 3-AR antagonists, respectively). (-)-Isoprenaline concentration-dependently relaxed circular muscle strips with an EC 50=0.32±0.06 μM. Such an effect was antagonized either by the contemporaneously presence of Betaxolol and ICI 11,855 [(-)-isoprenaline EC50=1.75±0.35 μM, pKB=7.88±0.10] or by Betaxolol, ICI 11,855 and SR 59230A [(-)-isoprenaline EC50=3. 49±0.38 μM, pKB=8.51±0.14]. Besides, SP-1f and SP-1h concentration-dependently relaxed circular muscle strips with an EC 50=0.35±0.07 μM and 0.45±0.12 μM, respectively. These values remained unchanged by blocking the 1- and 2-AR. The presence of SR 59230A antagonized the relaxing effect of SP-1f (EC50=3.51±0.94 μM, pKB=8.93±0.16) and did not modify the SP-1h relaxing potency. In colon circular smooth muscle and in mucosa, 3-AR mRNA expression levels were found to be 0.39±0.70 and 0.26±0.12 (P<0.05), respectively. Such results provide further evidence of the 3-adrenoceptor functional role in the human colon and the crucial contribution of SP-1f to the control of the gut dysmotility. © 2013 Elsevier B.V. All rights reserved

Gender-differences of in vitro colonic motility after chemo- and radiotherapy in humans

Abstract Background The aim of the present in vitro study was to investigate, in different genders, motor responses in surgical colonic specimens from patients with rectal cancer undergoing and not undergoing chemotherapy with capecitabine and radiotherapy. Methods This in vitro study was conducted from October 2015 to August 2017 at the Experimental Pharmacology Laboratory at the National Institute “S. de Bellis” after collecting samples at the Department of Surgery. Segments of sigmoid colon were obtained from 15 patients (Male (M)/Female (F) = 8/7; control group, CG) operated on for elective colorectal resection for rectal cancer without obstruction and 14 patients (M/F = 7/7; study group, SG) operated on for elective colorectal resection for rectal cancer who also received chemotherapy, based on capecitabine twice daily, and radiotherapy. Isometric tension was measured on colonic circular muscle strips exposed to increasing carbachol or histamine concentrations to obtain concentration-response curves. The motor responses to electrically evoked stimulation were also investigated. Results In males, carbachol and histamine caused concentration-dependent contractions in the CG and SG. An increased sensitivity and a higher response to carbachol and histamine were observed in SG than CG (P < 0.01). On the contrary, in females, the response to carbachol was not significantly different in CG from the SG and the maximal responses to carbachol were greater in CG than in SG (P < 0.001). The same applied to histamine for half-maximal effective concentrations and maximal response in that they were not significantly different in CG from the SG. Electrically evoked contractions were significantly more pronounced in males, especially in the SG (P < 0.05). Conclusions This preliminary in vitro study has shown gender differences in motor responses of colonic circular muscle strips in patients who had received chemotherapy with capecitabine and radiotherapy

Myogenic oxidative imbalance interferes with antral motility in obese subjects

Background: Obesity is characterized by a systemic low-grade chronic inflammatory oxidative condition that affects vascular and cardiac smooth muscle relaxation. In human antrum, relaxation is mediated by vasoactive intestinal peptide (VIP) through cAMP and cGMP signaling pathways. A genome-wide association study has demonstrated an association between VIP and obesity. Aim: To evaluate smooth muscle activity in human obese antrum, both in in vitro preparations as well as in vivo. Methods: Antral muscle strips and cells were isolated from surgical gastric samples from obese and normal weight subjects. Muscle contraction and relaxation, myogenic oxidative stress and inflammatory status were analyzed in vitro. Distal antral motility was evaluated in vivo by magnetic resonance imaging. Results: Obese antral muscle cells showed an oxidative-inflammatory imbalance with overexpression of NLRP3 inflammasome, increased IL-1 secretion and caspase1-activation, and reduced antioxidant capacity associated with a myogenic motor impairment of VIP-induced relaxation. The intracellular alterations were characterized by a decreased activation of the cAMP-signaling pathway and a decreased expression of eNOS. These in vitro alterations coincided with the hindering of antral motor activity observed in vivo. Apocynin treatment, counteracting oxidative stress, reverted alterations observed in obese antral muscle. Conclusion: Antral myogenic activity of obese subjects can be impaired by alterations of signaling pathways induced by oxidative stress