Modulation by the Muscarinic Agonist McN-A-343 of Noradrenaline Release from Vascular Sympathetic Neurones

Interaction of some muscarinic agonists and antagonists at the prejunctional muscarinic receptor in the rabbit ear artery preparation

“…Evidence that the prejunctional receptor site in the ear artery may differ from other muscarinic receptors in its interaction with antagonists comes from findings with 4-DAMP. This muscarinic receptor antagonist, has been reported previously to show selectivity for ileal muscarinic receptors over cardiac muscarinic receptors (Barlow et al, 1976;1980). In our hands using carbachol as the agonist, it exhibited an affinity in the ear artery significantly lower than that observed for either guinea-pig atria (pKB,8.45) or ileal longitudinal muscle (pKB, 9.07) (Choo & Mitchelson, 1985b).…”

“…The affinity is also lower than that reported in rabbit myometrium (pKB 8.50; agonist, methacholine) (Crankshaw, 1984) or rat anococcygeus muscle (pKB,8.75;acetylcholine) (Oriowo, 1983). However, low values have been obtained for 4-DAMP in the atria in the absence (pK5, 7.90, carbachol) (Eglen et al, 1984, quoted in Eglen & Whiting, 1985 or presence of hexamethonium (pKB, 7.79, carbachol) (Barlow et al, 1976;1980).…”

“…Other studies have indicated that there may be differences in the responsiveness of this prejunctional receptor to agonists compared to prejunctional muscarinic receptors on other sympathetic nerves in the rabbit, as McN-A-343 is a potent agonist on the receptors in the ear artery (Rand & Varma, 1971) but not in the heart (Fozard & Muscholl, 1972) or pulmonary artery (Nedergaard, 1980;1981). Furthermore, the muscarinic receptor antagonist, pirenzepine, was a more potent inhibitor of responses to McN-A-343 in the ear artery than of those to carbachol (Choo et al, 1985).…”

“…Additionally, the effectiveness of two selective muscarinic antagonists, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) and and secoverine were determined. The former has been reported to exhibit selectivity for muscarinic receptors in ileum over those in atrial tissue (Barlow el al., 1976;1980) while the latter has selectivity for muscarinic receptors in intestinal smooth muscle compared to those in glandular tissue (Zwagemakers & Claassen, 1980;1981).…”

Effect of ω‐Conotoxin GVIA on Noradrenaline Release from Postganglionic Sympathetic Neurones in Rabbit Aorta

“…A preliminary account of this investigation was presented at the XIIIth International Congress of Pharmacology, Munich (Nedergaard 1998). (Nedergaard 1980;Jensen & Nedergaard 1999) was used. Albino rabbits (1.8-2.5 kg) of either sex were sacrificed by cervical dislocation and exsanguinated.…”