Characterization of the central muscarinic cholinoceptors involved in the cholinergic pressor response in anesthetized dogs.
Previous reports have shown that an intracisternal (i.c.) injection of acetylcholine in the dog increases both arterial blood pressure and plasma levels of noradrenaline and vasopressin via central muscarinic receptors. The aim of the present study was to characterize the central muscarinic cholinoceptor subtypes involved in such central cholinergic responses in anesthetized male Beagle-Harrier dogs (n = 12). For this purpose, we studied the relative potency of various muscarinic receptor antagonists to block the acetylcholine-induced pressor responses (30 microg kg(-1) i.c.). The acetylcholine-induced pressor response was inhibited in a dose-dependent manner by the i.c. administration of the non-selective muscarinic receptor antagonist atropine (ID50 = 0.5 microg kg(-1)), the muscarinic M receptor antagonist pirenzepine (ID50 = 0.45 microg kg(-1)), the muscarinic M2 receptor antagonist methoctramine (ID50 = 8.5 microg kg(-1)) and the muscarinic M3 receptor antagonist para-fluoro-hexahydro-sila-difenidol (ID50) = 43.7 microg kg(-1)). The order of potency of these four muscarinic receptor antagonists was: atropine = pirenzepine > methoctramine >> para-fluoro-hexahydro-sila-difenidol. In order to confirm the selectivity for muscarinic M1 receptors of this dose of pirenzepine, we checked that 40- to 50-fold higher concentrations were necessary to block a typical muscarinic M2 receptor response (bradycardia) and a typical muscarinic M3 receptor response (endothelial vasodilation) compared with methoctramine and para-fluoro-hexahydro-sila-difenidol, respectively. These results suggest that the pressor response elicited by intracisternal injection of acetylcholine in anesthetized Beagle-Harrier dogs is mediated through the activation of the muscarinic M1 cholinoceptor subtype.
Pelat
M
M
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317 et U455, Faculté de Médecine, Toulouse, France.
Lazartigues
E
E
Tran
M A
MA
Gharib
C
C
Montastruc
J L
JL
Montastruc
P
P
Rascol
O
O
D000109:Acetylcholine / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003959:Diamines / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood / Q000187:drug effects
D003959:Diamines; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D014665:Vasodilator Agents; D014667:Vasopressins; D001285:Atropine; D000109:Acetylcholine; C054938:methoctramine; D009638:Norepinephrine