Biphasic dose-response curve to muscarine on the rat superior cervical ganglion.

Abstract

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.

• Authors: N R Newberry, M J Gilbert
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 163 Issue 2-3 Pg. 237-44 (Apr 25 1989) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2721572 (Publication Type: Journal Article)

Chemical References

• Virulence Factors, Bordetella
• Pirenzepine
• Muscarine
• Pertussis Toxin
• otenzepad
• Gallamine Triethiodide

Topics

• Animals
• Dose-Response Relationship, Drug
• Gallamine Triethiodide (pharmacology)
• Ganglia, Spinal (drug effects)
• In Vitro Techniques
• Muscarine (pharmacology)
• Pertussis Toxin
• Pirenzepine (analogs & derivatives, pharmacology)
• Rats
• Virulence Factors, Bordetella (pharmacology)