主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Background: Serotonine influences the contractility of organ bath isolated intestine harvested from rats in which the endogene deposits of serotonine have been exhausted through administration of paraclorphenylalanine (PCPA). Serotonine raises: contraction force, contraction force evolution speed during contraction and contraction force evolution speed during relaxation in a dose-dependent manner and modulates acetylcholine contractility influence.
Materials, methods: Eight samples; intestines harvested from rats preatreated with PCPA dissolved in Tween 80 administered intraperitoneally. Dosage: 300 mg/kg bw/day/three days. Samples were introduced in organ bath in aerated Tyrode solution and maintained at a constant 37C temperature. Each sample, with the help of an isometric electromecanic transducer, has shown a computer-registered value for contractile activity. Computer analysis of data has determined sample contraction-force, measured in gramsforce, contraction force evolution speed during contraction and contraction force evolution speed during relaxation, measured in gramsforce/second for every concentration pair. We have administered granisetron as to obtain in the organ bath concentrations of 10-8M, 10-7M, 10-6M and 10-5M. For each concentration there have been doses of serotonine as to obtain in organ bath concentrations of 10-8M, 10-7M, 10-6M, 10-5M and 10-4M. We used tStudent test for statistic significance of differences. Statistically significant differences were for which p<0.05. Results: Granisetron has antagonised the growth of contraction force produced by serotonine for every concentration equal to or higher than 10-7M granisetron.
Granisetron has antagonised serotonine's effect of contraction force evolution speed growth during contraction for every concentration starting with 10-7M granisetron and higher. Contraction force evolution speed during relaxation has been antagonised by concentrations of granisetron higher than 10-6M. So, serotonine influences the analysed parameters: contraction force, contraction force evolution speed during contraction and contraction force evolution speed during relaxation through 5-HT3 receptors.
Conclusions: Experimental data shown that serotonine, whilst its intestinal concentrations are getting higher because of SSRI administration, can result in intestinal contractions that translate into nausea, regurgitations and bowel movement anomally that usually appear when SSRI are administered. Due to the fact that 5-HT3 receptors modulate the former, we wanted to show that granisetron administration can eliminate these intestinal adverse effects of SSRI.