Functional characterization of peripheral muscarinic subtypes in anesthetized cats.
This investigation was undertaken to characterize the muscarinic receptor subtypes involved in methacholine-induced vasodilation, vagal bradycardia, neurally-evoked sudomotor responses and sympathetic muscarinic ganglionic transmission in anesthetized cats. Dose-response curves were constructed using the putatively selective antagonists pirenzepine (M1), gallamine (M2) and 4-DAMP (M3: 4-diphenyl-acetoxy-N-methylpiperidine) and compared with the non-selective blocker, atropine. Methacholine hypotension and evoked sudomotor responses exhibited an M3 muscarinic receptor profile with the following potency relationships: atropine > or = 4-DAMP > pirenzepine >> gallamine. Vagal bradycardia (M2) was antagonized by gallamine and exhibited a lower relative sensitivity to 4-DAMP when corrected for atropine effect. Pirenzepine was inactive in inhibition of bradycardia but was highly potent against transmission in the sympathetic ganglion (M1) with the following potency relationships: atropine > or = pirenzepine > 4-DAMP >> gallamine. In comparison with atropine, 4-DAMP exhibited a significantly lower potency for M1 and M2 muscarinic receptors as compared to its effect on the M3 muscarinic receptor subtypes.
Koss
M C
MC
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D005703:Gallamine Triethiodide / Q000494:pharmacology; D005712:Galvanic Skin Response / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D005703:Gallamine Triethiodide