title: Urethane, but not pentobarbitone, attenuates presynaptic receptor function in rats: a contribution to the choice of anaesthetic.
abstract: 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.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
authors.forename: Cm
authors.initials: C
authors.lastname: Kurz
authors.forename: U
authors.initials: U
authors.lastname: Baranowska
authors.forename: S
authors.initials: S
authors.lastname: Lupiński
authors.forename: M
authors.initials: M
authors.lastname: Göthert
authors.forename: B
authors.initials: B
authors.lastname: Malinowska
authors.forename: E
authors.initials: E
authors.lastname: Schlicker
mesh_terms: 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
chemical_list: 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
references.citation: Br J Pharmacol. 2003 Sep;140(2):323-8
references.pmid: 12970076
references.citation: Eur J Pharmacol. 1991 Dec 3;205(3):307-10
references.pmid: 1667915
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):639-46
references.pmid: 1353253
references.citation: Experientia. 1986 Feb 15;42(2):109-14
references.pmid: 2868911
references.citation: Neurosci Lett. 1997 Nov 28;238(1-2):84-6
references.pmid: 9464661
references.citation: Toxicol Appl Pharmacol. 1983 May;68(3):354-8
references.pmid: 6857669
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1993 Jul;348(1):35-45
references.pmid: 8397342
references.citation: Br J Pharmacol. 2000 May;130(2):321-30
references.pmid: 10807669
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2001 Sep;364(3):233-41
references.pmid: 11521166
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1999 Jun;359(6):466-70
references.pmid: 10431757
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1992 Apr;345(4):489-93
references.pmid: 1352385
references.citation: J Pharmacobiodyn. 1988 Jan;11(1):18-30
references.pmid: 3385601
references.citation: Proc Soc Exp Biol Med. 1947 Apr;64(4):453-5
references.pmid: 20239456
references.citation: J Pharmacol Exp Ther. 1982 Nov;223(2):524-35
references.pmid: 6127404
references.citation: Pharmacol Rev. 2002 Jun;54(2):323-74
references.pmid: 12037145
references.citation: Anesth Analg. 2002 Feb;94(2):313-8, table of contents
references.pmid: 11812690
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1989 Dec;340(6):633-8
references.pmid: 2615855
references.citation: Br J Pharmacol. 1973 Apr;47(4):850-2
references.pmid: 4723805
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1995 Jul;352(1):43-8
references.pmid: 7477424
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1997 Feb;355(2):261-6
references.pmid: 9050021
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1994 Jan;349(1):20-4
references.pmid: 7908122
references.citation: Experientia. 1986 Mar 15;42(3):292-7
references.pmid: 3007197
references.citation: Br J Pharmacol. 1996 Aug;118(8):2023-8
references.pmid: 8864538
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1993 Nov;348(5):498-503
references.pmid: 8114949
references.citation: J Pharmacol Exp Ther. 2008 Sep;326(3):912-9
references.pmid: 18567834
references.citation: Biochem J. 1949;44(5):528-31
references.pmid: 16748559
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1979 Aug;308(2):127-36
references.pmid: 228207
references.citation: J Auton Nerv Syst. 1998 Aug 6;72(1):46-54
references.pmid: 9760079
references.citation: Br J Pharmacol. 2008 Mar;153 Suppl 2:S1-209
references.pmid: 18347570
references.citation: Brain Res Bull. 1998 Sep 15;47(2):129-32
references.pmid: 9820729