Yüksel Kesim

The antinociceptive effects of intravenous tianeptine in colorectal distension-induced visceral pain in rats: The role of 5-HT3 Receptors.

Tianeptine is an unusual tricyclic antidepressant drug. In this study, we aimed to investigate the antinociceptive effect of tianeptine on visceral pain in rats and to determine whether possible antinociceptive effect of tianeptine is mediated by serotonergic (5-HT(2,3)) and noradrenergic (α(1,2)) receptor subtypes. Male Sprague Dawley rats (250-300 g) were supplied with a venous catheter, for drug administrations, and enameled nichrome electrodes, for electromyography, at external oblique musculature. Colorectal distension (CRD) was employed as the noxious visceral stimulus and the visceromotor response (VMR) to CRD was quantified electromyographically before and 5, 15, 30, 60, 90 and 120 min after tianeptine administration. Antagonists were administered 10 min before tianeptine for their ability to change tianeptine antinociception. Intravenous administration of tianeptine (2.5-20 mg/kg) produced a dose-dependent reduction in VMR. Administration of 5-HT(3) receptor antagonist ondansetron (0.5, 1 and 2 mg/kg), but not 5-HT(2) receptor antagonist ketanserine (0.5, 1 and 2 mg/kg), reduced the antinociceptive effect of tianeptine (10mg/kg). In addition, administration of α(1)-adrenoceptor antagonist prazosin (1 mg/kg) or α(2)-adrenoceptor antagonist yohimbine (1 mg/kg) did not cause any significant effect on the tianeptine-induced antinociception. Our data indicate that intravenous tianeptine exerts a pronounced antinociception against CRD-induced visceral pain in rats, and suggests that the antinociceptive effect of tianeptine appears to be mediated in part by 5-HT(3) receptors, but does not involve 5-HT(2) receptors or α-adrenoceptors.

Possible role of sildenafil in inhibiting rat vas deferens contractions by influencing the purinergic system

Abstract

The antinociceptive effect of intravenous imipramine in colorectal distension-induced visceral pain in rats: The role of serotonergic and noradrenergic receptors☆ , ☆☆

It has been shown that imipramine, a tricyclic antidepressant (TCA), is a potent analgesic agent. However, the effect of imipramine on visceral pain has not been extensively investigated. In the current study, our aim was to characterise the putative analgesic effect of intravenous imipramine on visceral pain in rats. Our second aim was to assess the involvement of serotonergic (5-HT₂,₃,₄) and noradrenergic (α(2A, 2B, 2C)) receptor subtypes in this putative antinociceptive effect of imipramine. Male Sprague Dawley rats (250-300 g) were implanted with venous catheters for drug administration and implanted with enamelled nichrome electrodes for electromyography of the external oblique muscles. Noxious visceral stimulation was applied via by colorectal distension (CRD). The visceromotor responses (VMRs) to CRD were quantified electromyographically before and after imipramine administration at 5, 15, 30, 60, 90 and 120 min. In the antagonist groups, the agents were administered 10 min before imipramine. The administration of imipramine (5-40 mg/kg) produced a dose-dependent reduction in VMR. The administration of yohimbine (a nonselective α₂-adrenoceptor antagonist, 1 mg/kg), BRL-44408 (an α(2A)-adrenoceptor antagonist, 1 mg/kg) or MK-912 (an α2C-adrenoceptor antagonist, 300 μg/kg) but not imiloxan (an α(2B)-adrenoceptor antagonist, 1 mg/kg) inhibited the antinociceptive effect of imipramine (20 mg/kg). Additionally, ketanserin (a 5-HT₂ receptor antagonist, 0.5, 1, and 2 mg/kg) and GR113808 (a 5-HT₄ receptor antagonist, 1 mg/kg) enhanced, and ondansetron (a 5-HT₃ receptor antagonist, 0.5, 1, and 2 mg/kg) failed to alter the imipramine-induced antinociceptive effect. Our data demonstrated that, in the CDR-induced rat visceral pain model, intravenous imipramine appeared to have antinociceptive potential and that α(2A)-/α(2C)-adrenoceptors and 5-HT₂/5-HT₄ receptors may be responsible for the antinociceptive effect of imipramine on visceral pain in rats.

Non-Steroidal Anti-İnflamatuar İlaçların İzole Sıçan Mesanesi Detrüsör Striplerine Etkisi

OZET Bu calismada farkli gruplardan non-steroidal anti-inflamatuar ilaclarin (NSAII) mesane kas motilitesinin duzenlenmesine katilan cesitli fizyolojik mekanizmalar uzerindeki etkileri izole sican mesanesi detrusor striplerinde incelendi. Bu amacla; aspirin, indometazin ve ketoprofen varliginda izole detrusor striplerinin karbakol, isoprenalin ve elektriksel alan stimulasyonu (EAS)’na verdigi yanitlar degerlendirildi. In vitro calismalar icin, mesane detrusor kaslari cikarilarak organ banyolarina asildi. Deney protokolunun baslangicinda, detrusor kaslarinin karbakol, isoprenalin ve EAS’ye verdigi yanitlar kontrol yanitlari kabul edilerek kaydedildi. Daha sonra, bu yanitlar NSAII’lar ile 30 dakika muamelenin (inkubasyon) ardindan tekrar alindi. Her bir NSAII varliginda mesane bazal tonuslarinda meydan gelen degisiklikler de degerlendirildi. Aspirin varliginda mesane bazal tonusu degismedi. Dusuk konsantrasyonlarda aspirin (10-8M ve 10-7M) detrusor striplerinin karbakole verdigi yanitlari anlamli olarak azaltti, fakat daha yuksek konsantrasyonlarda (10-6-10-4M) kontrol yanitlari ile karsilastirildiginda anlamli fark bulunmadi. Isoprenalin yanitlari, aspirin (10-7-10-5M) varliginda degismedi. Aspirin, sadece en dusuk konsantrasyonda (10-7M) EAS’nun yuksek frekansli yanitlarini anlamli olarak azaltti, fakat dusuk frekansli yanitlarini degistirmedi. Bununla birlikte, daha yuksek konsantrasyonlarda (10-6M, 10-5M) EAS yanitlari uzerinde etkili bulunmadi. Indometazin varliginda (10-7-10-5M) bazal tonus azaldi. Karbakol ve EAS yanitlari degismedi. Isoprenalin yanitlari indometazin ile muamelenin ardindan doz bagimli olarak azaldi. Ketoprofen (10-7-10-5M) ile inkubasyon bazal tonusta dususe neden oldu ve karbakol yanitlarini anlamli olarak artirdi. Sadece en yuksek ketoprofen konsantrasyonu isoprenalin yanitlarini anlamli olarak azaltti. Ketoprofen kullanilan dozlarin hicbirinde EAS yanitlarini degistirmedi. Sonuclarimiz, izole detrusor striplerinde NSAII’lar varliginda karbakol, isoprenalin ve EAS yanitlarinda meydana gelen degisikliklerin temel olarak prostaglandin sentez inhibisyonu ile iliskili oldugunu gostermektedir. Ancak diger mekanizmalarin katkisi da goz ardi edilmemelidir. Bununla birlikte, farkli gruplardan NSAII’larin bu yanitlar uzerindeki etkileri birbirlerinden farklidir. The effects of non-steroidal anti-inflammatory drugs on isolated rat bladder detrusor strips ABSTRACT In this study, the effects of non-steroidal anti-inflammatory drugs (NSAIDs) from different groups on various physiological mechanisms involving bladder muscle motility were investigated in isolated rat detrusor strips. For this purpose, in the presence of aspirin, indomethacin and ketoprofen the responses of isolated detrusor strips to carbachol, isoprenalin, and electrical field stimulation (EFS) were evaluated. For in vitro studies, bladder detrusor muscles were removed and placed in organ baths. At the beginning of experimental protocol, the responses of detrusor strips to carbachol, isoprenalin and EFS were taken as control responses and recorded. Subsequently, following 30 minutes incubation with NSAIDs these responses were recorded again. The changes that occur in bladder basal tone in the presence of each NSAIDs were also assessed. In the presence of aspirin basal tone did not change. Aspirin at low concentrations (10-8M and 10-7M) significantly reduced detrusor responses to carbachol. But, at the higher concentrations (10-6-10-4M) when compared with control responses there was no significant difference. Isoprenalin-evoked responses were not changed in the presence of aspirin (10-7-10- 5M). Only, the lowest aspirin concentration (10-7M) significantly reduced the high frequencies of EFS-evoked responses, but the low frequencies of EFS-evoked responses left unchanged. Furthermore, at the higher concentrations (10-6M, 10-5M) of aspirin did not change EFS-evoked responses. In the presence of indomethacin (10-7-10-5M) basal tone reduced and carbachol- and EFS-evoked responses did not change. The detrusor responses to isoprenalin significantly reduced dose-dependant way after incubation with indomethacin. Incubation with ketoprofen (10-7-10-5M), caused a fall in basal tone and significantly enhanced carbachol-evoked responses. Only the highest ketoprofen concentration significantly inhibited isoprenalin-evoked responses. Ketoprofen, at the doses used, did not change EFS-evoked responses. Our results show that; the effects of NSAIDs on isolated detrusor strips are mainly due to prostaglandin synthesis inhibition but contribution of other mechanisms can not be ruled out. Furthermore, effects of NSAIDs from different on these responses are different from each other. J. Exp. Clin. Med., 2011; 28:71-78

Motor Eşgüdümünde Dopaminerjik Sistemin Rolü

The Role of Dopaminergic System in Motor Coordination Previous studies have demonstrated that dopamine (DA) receptor agonists enhanced locomotor activity. The present study was designed to determine the relative contribution of Di and D2 (DA) receptor subtypes in motor coordination. Apomorphine, a nonselective dopamine receptor agonist, decreased motor coordination at the doses of 0.125 and 0.25 mg/kg, but increased the motor coordination at 0.5 and 1 rng/kg. The D2 dopamine receptor antagonists, sulpiride (50 mg/kg) and spiperone (40 pg/kg). decreased motor coordination when administrered either alone or combination with apomorphine (0.5 mg/kg). Selective Di receptor agonist SKF 81297 (10 mg/kg) enhanced motor coordination. The effect of SKF 81297 was antagonized by lluphenazine (0.125 mg/kg). The D2 receptor agonist bromocriptine (5. 1 0. 20. 30 mg/kg) significantly increased motor coordination. The effect of bromocriptine (10 rng/kg) was inhibited when administered either sulpirid (50 mg/kg) or c/.-methyl p-tyrosine prior to bromocriptine. These data demonstrated that both Dj and D2 receptors may involved in motor coordination Yapilan calismalar santral sinir sisteminde dopaminerjik aktiviteyi artiran ilaclarin motor aktiviteyi artirdigini gostermistir. Bu calismada motor esgudumde dopamiii reseptorlerinin rolu doner-cubuk dayaniklilik (rotarod performans) yontemi ile arastirilmistir. Secici olmayan dopamin agonisti apomorfin, sicanlarin rotarod performansini dusuk dozlarda (0.125 - 0.25 mg/kg) azaltmis, yuksek dozlarda (0.5-1 mg/kg) ise artirmistir. Apomorfin ile olusan rotarod performans artisi secici olmayan DA antagonist! flufenazin (0.125 iiig/ kg), secici D2 antagonislleri sulpirid (50 mg/kg) ve spiperon (40 pg/kg ) ile onlenmistir. Secici D[ agonisfi SKF 81297 (10 mg/kg) rotarod performansi anlamli olarak artirmis ve bu artis flufenazin (0.125 mg/kg) ile onlenmistir. Secici D2 agonist i bromokriptin (5. 10. 20, 30 mg/kg) rotarod performansi artirmis ve bu artislar secici D2 antagonisu sulpirid (50 mg/kg) ve dopamin sentez inhibitoru a-metil p-Urozin ile onlenmistir. Bu calismanin bulgulari hem D] hem de. D2 dopamin reseptorlerinin motor esgudumde rol oynayabilecegini gostermektedir.