Urethane, but not pentobarbitone, attenuates presynaptic receptor function in rats: a contribution to the choice of anaesthetic

Abstract

Background and purpose:We examined whether cannabinoid CB1 and histamine H3 receptors resemble a2-adrenoceptors in that their presynaptically mediated cardiovascular effects are less marked in urethane-than in pentobarbitone-anaesthetized pithed rats. Experimental approach: Effects of the cannabinoid agonist CP-55,940 and the H3 receptor agonist imetit on electrically induced tachycardic and vasopressor responses, respectively, was compared in pithed rats anaesthetized with urethane or pentobarbitone. The affinity of urethane for the three receptors was measured by radioligand binding studies in rat brain cortex membranes and its potency assessed in superfused mouse tissues preincubated with 3 H-noradrenaline. Key results: The neurogenic tachycardic response was less markedly inhibited by CP-55,940 in urethane-than in pentobarbitone-anaesthetized pithed rats. Imetit inhibited the neurogenic vasopressor response after pentobarbitone but not after urethane. The catecholamine-induced tachycardic and vasopressor response did not differ between rats anaesthetized with either compound. Urethane 10 mM (plasma concentration reached under anaesthesia) did not affect binding to CB1 or H3 receptors and a2 adrenoceptors, nor did it alter the inhibitory effect of agonists at the three receptors on electrically evoked 3 H-noradrenaline release. Conclusions and implications:Urethane, but not pentobarbitone, abolished the H3 receptor-mediated vascular response in pithed rats and attenuated the CB1 receptor-mediated cardiac response much more than pentobarbitone. The weaker effects of CB1, H3 and a2 receptor agonists cannot be explained by antagonism by urethane at the three receptors in vitro. Pentobarbitone, but not urethane, is suitable as an anaesthetic for investigations of inhibitory presynaptic receptor function in pithed and anaesthetized rats. (2009) British Journal of Pharmacology IntroductionPithed animals offer the opportunity to study the influence of pre- (Armstrong and Boura, 1973) and postsynaptic receptors (Shipley and Tilden, 1947) on cardiovascular parameters under conditions that resemble the in vivo situation in many respects. One major advantage of such preparations is the fact that basal blood pressure and heart rate (HR) are very stable since they are no longer under the control of reflex loops involving the central nervous system (CNS). Prior to pithing, the animals have to be anaesthetized. The choice of the anaesthetic is of crucial importance on the effect of test drugs on cardiovascular parameters studied later in the pithed animal. For instance, in pithed rats the cardiovascular responses to a2-adrenoceptor agonists acting at pre-and postsynaptic a2-adrenoceptors wereCorrespondence: E Schlicker,

Enhanced function of inhibitory presynaptic cannabinoid CB1 receptors on sympathetic nerves of DOCA–salt hypertensive rats

“…The rats were anaesthetised with pentobarbitone, which unlike urethane does not attenuate the function of presynaptic receptors [18]. Like in our previous studies [12,36], we used pithed and vagotomised rats because we wanted to study peripheral mechanisms only.…”

Interaction between urethane and cannabinoid CB1 receptor agonist and antagonist in penicillin-induced epileptiform activity

“…Urethane has been widely used as an anesthetic in combination with a number of different chemicals in experimental epilepsy studies (Rose 1979, Campbell and Holmes 1984, Largo et al 1997, Cakil et al 2011, Erfanparast and Tamaddonfard 2015. The choice of anesthetic is crucial, as it may interact with test drugs with regard to of some of the parameters studied in in vivo experiments (Chesher et al 1974, Kurz et al 2009, Hunfeld et al 2013). The present study shows that the doses of penicillin required to induce epileptiform activity were higher in urethane-anesthetized rats than in conscious rats, and that there was no interaction between urethane and the cannabinoid CB1 receptor agonist, ACEA, and the antagonist, AM-251, regarding their effects on penicillin-induced epileptiform activity.…”

“…Unfortunately, we could not compare these results with those of other studies, as there are no available data regarding the interaction of anesthetics with cannabinoid receptors in experimental models of epilepsy. However, a few studies have shown an interaction between anesthetic and cannabinoids in biological responses (Baranowska et al 2008, Kurz et al 2009). The cannabinoid receptor agonist methanandamide inhibited electrically induced tachycardia, which was eliminated by the CB1 receptor antagonist AM-251 in pentobarbitone-anesthetized pithed rats, but not in urethane-anesthetized pithed rats (Baranowska et al 2008).…”

“…Kurz and others (2009) suggested that the cannabinoid receptor agonist CP-55,940 inhibited the neurogenic tachycardic response to a more marked extent in pentobarbitone-anesthetized pithed rats than in urethane-anesthetized pithed rats, emphasizing that the effects of agonists acting via cannabinoid CB1 receptors crucially depend on the anesthetic selection. This therefore suggests that pentobarbitone is better suited than urethane as an anesthetic in investigating inhibitory presynaptic receptor function in the sympathetic nerve terminals of pithed rats (Kurz et al 2009). …”

Acute Myocardial Infarction Inhibits the Neurogenic Tachycardic and Vasopressor Response in Rats via Presynaptic Cannabinoid Type 1 Receptor

“…Because an inhibitory effect of MI occurred, we studied which types of cannabinoid or cannabinoid-like receptors are involved and whether the effect can be increased by the blockade of endocannabinoid-degrading enzymes. Rats were anesthetized with pentobarbitone, which, unlike urethane, does not attenuate the function of presynaptic receptors (Kurz et al, 2009). The electrically induced increases in HR and BP studied in pithed rats are associated predominantly with catecholamines released from the neuronal sympathetic nerve endings of the heart and vessels (data not shown).…”