Biphasic dose-response curve to muscarine on the rat superior cervical ganglion.
The dose-response curve for the muscarine-induced depolarisation of the rat isolated superior cervical ganglion, studied over the concentration range of 3 nM-1 mM, was biphasic. An apparent maximum was obtained at around 1-3 microM muscarine, but this was only a plateau between the two parts of the curve. Two cardioselective antagonists, gallamine (10 microM) and AF-DX 116 (1 microM) had a complex action on this dose-response curve. The dose-response curve between 0.01 and 0.3 microM was shifted to the right, the responses around 3 microM muscarine were enhanced, but the dose-response curve over 30 microM muscarine was unaffected. The M1-selective antagonist pirenzepine (0.05 microM) depressed all parts of the dose-response curve, but it still appeared biphasic. Pretreatment of the ganglion with pertussis toxin (1 microgram/ml) enhanced the depolarisation to muscarine 0.01-1000 microM and the dose-response curve became less biphasic. Like gallamine and AF-DX 116, pertussis toxin abolished the muscarinic M2-mediated hyperpolarisation of the ganglion recorded in 0.3 microM pirenzepine. It is concluded that the presence of an underlying M2-mediated hyperpolarisation contributes to the biphasic nature of the dose-response curve to muscarine.
Newberry
N R
NR
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, U.K.
Gilbert
M J
MJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005703:Gallamine Triethiodide / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects*; D066298:In Vitro Techniques; D009116:Muscarine / Q000494:pharmacology*; D037342:Pertussis Toxin; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D010890:Pirenzepine; D009116:Muscarine; D037342:Pertussis Toxin; C048593:otenzepad; D005703:Gallamine Triethiodide