Subtypes of muscarinic receptor on cholinergic nerves and atrial cells of chicken and guinea‐pig hearts

Abstract

1 Electrically driven chicken and guinea-pig atria were used to investigate the negative inotropic effects of the muscarinic agonists methacholine and acetylcholine (ACh). The release of ACh from isolated hearts into the perfusate in response to (preganglionic) vagal or (pre-and postganglionic) field stimulation was bioassayed on the guinea-pig ileum or determined by labelling with ['H]-choline. (Pz) and atropine were 40 and 5.4 nmol -'in chicken atria and 330 and 3.5 nmol '-', respectively, in guineapig atria. Thus, the respective potency ratios (IC0pJIC5j,trope) were 7.4 and 94.3 in the two species.3 Pirenzepine in low concentrations increased the release of unlabelled and 'H-labelled ACh from isolated hearts evoked by vagal and field stimulation only in chicken, but not in guinea-pigs. The halfmaximally-effective concentration of pirenzepine was about 30 nmol I' in the chicken heart, whereas, in the guinea-pig heart, an increased release was observed at 300 nmol I-'. (+ )-Tubocurarine [(+ )-Tc; 100 pmol I-'] reduced the release of ACh evoked by (preganglionic)vagal stimulation to a (+ )-Tc-resistant release of about 30%. The time-course of the neuronal release of['H]-ACh was markedly altered: the onset was delayed and the termination was extended beyond the period of stimulation ( min or 5 s) by several seconds. The (+)-Tc-resistant release was nearly abolished by 30 nmol I' pirenzepine. 5 In conclusion, the pre-and post-synaptic muscarinic receptors of the parasympathetic neuroeffector junction of the heart both belong to the M,-subtype in the chicken and to an M2-subtype in the guinea-pig. Block of the nicotinic ganglionic transmission in the chicken heart by (+ )-Tc unmasked a muscarinic transmission, which presumably was mediated through M,-receptors stimulating a low and prolonged postganglionic release of ACh.

Presynaptic muscarinic receptors mediating inhibition of neurogenic contractions in rabbit vas deferens are of the ganglionic M1-type

“…Presynaptie M 1 -receptors have also been found in ehieken heart (Jeck et al, 1988), different guinea-pig and rat brain areas (Belleroehe and Gardiner, 1985;Marehi et al, 1986;Williams and Constanti, 1988) as weil as in guinea-pig and rat small intestine (Mieheletti et al, 1988;Sehwörer and K.ilbinger, 1988). However, it remains to be elueidated whether all these presynaptie musearlnie reeeptors are pharmacologieally identieal or whether they belang to different M 1 -reeeptor subclasses.…”

Effect of pirenzepine and gallamine on cardiac and pulmonary muscarinic receptors in the rabbit

“…Such receptors have previously been described in the cardiac nerves in the rat (Wetzel & Brown, 1985) and in the guinea-pig (Jeck et al, 1988). Blockade of these receptors by gallamine would increase transmitter output from the vagus nerves and increase the concentration of antagonist required to inhibit vagallyinduced bradycardia.…”

“…At present, the guinea-pig is the only species in which M2 receptors have been demonstrated in both pulmonary (Fryer & Maclagan, 1984) and cardiac (Jeck et al, 1988) parasympathetic nerves.…”

Two populations of muscarinic binding sites in the chick heart distinguished by affinities for ligands and selective inactivation

“…The high affinity of chick cardiac receptors for pirenzepine has been observed repeatedly (Brown et al, 1985;Lindmar & Loffelholz, 1987;Jeck et al, 1988;Choo et al, 1988;Lazareno et al, 1990;Tietje & Nathanson, 1991), although low affinity was found by Sorota et al (1986). (2) The M2-like sites in chick heart have a slightly lower Kd for NMS than the M4-like population, while in mammalian tissues, the affinity of M4 receptors for NMS is higher than that of M2 receptors (Waelbroeck et al, 1990;Lazareno et al, 1990).…”

“…They appear similar to the Ml subtype because of their high affinity for pirenzepine (Brown et al, 1985;Lindmar & Loffelholz, 1987;Jeck et al, 1988), but the pattern of affinities of other ' Author for correspondence.…”