Urethane, but not pentobarbitone, attenuates presynaptic receptor function in rats: a contribution to the choice of anaesthetic.
OBJECTIVE
We examined whether cannabinoid CB(1) and histamine H(3) receptors resemble alpha(2)-adrenoceptors in that their presynaptically mediated cardiovascular effects are less marked in urethane- than in pentobarbitone-anaesthetized pithed rats.


METHODS
Effects of the cannabinoid agonist CP-55,940 and the H(3) 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.


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 CB(1) or H(3) receptors and alpha(2) adrenoceptors, nor did it alter the inhibitory effect of agonists at the three receptors on electrically evoked (3)H-noradrenaline release.


CONCLUSIONS
Urethane, but not pentobarbitone, abolished the H(3) receptor-mediated vascular response in pithed rats and attenuated the CB(1) receptor-mediated cardiac response much more than pentobarbitone. The weaker effects of CB(1), H(3) and alpha(2) 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.
Kurz
Cm
C
Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Baranowska
U
U
Lupiński
S
S
Göthert
M
M
Malinowska
B
B
Schlicker
E
E
D058647:Adrenergic alpha-2 Receptor Agonists; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology; D003655:Decerebrate State; D004558:Electric Stimulation; D017442:Histamine Agonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010424:Pentobarbital / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000502:physiology; D017661:Receptors, Presynaptic / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014520:Urethane / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D000777:Anesthetics; D003511:Cyclohexanols; D017442:Histamine Agonists; D007093:Imidazoles; D043884:Receptor, Cannabinoid, CB1; D017661:Receptors, Presynaptic; D014662:Vasoconstrictor Agents; D014520:Urethane; C077430:imetit; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D013890:Thiourea; D010424:Pentobarbital
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