A presynaptic excitatory M1 muscarine receptor at postganglionic cardiac noradrenergic nerve fibres that is activated by endogenous acetylcholine

Abstract

Rabbit atria were isolated with the extrinsic right vagus and sympathetic nerves intact and perfused with Tyrode solution. Noradrenaline overflow evoked by sympathetic nerve stimulation (SNS) at 3 Hz for 3 min was determined before, during, and after vagus nerve stimulation (VNS), also at 3 Hz and for 3 min. The VNS pulses preceded the SNS pulses by 3, 100 and 233 ms. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline. Pirenzepine 80 nmol/l failed to alter the muscarinic inhibition of noradrenaline overflow when the vago-sympathetic impulse intervals were 3 and 233 ms. At an interval of 100 ms VNS did not significantly inhibit noradrenaline overflow in the absence of pirenzepine but produced an inhibition in the presence of the drug. When the pirenzepine concentration was varied (0.4-300 nmol/l) the largest inhibition of noradrenaline overflow was observed at 5.7 nmol/l whereas 300 nmol/l fully antagonized the inhibition. Acetylcholine overflow evoked by VNS was not altered by pirenzepine 0.4-300 nmol/l. AF-DX 116 (11-[(2[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5, 11-dihydro-6H-pyrido-[2,3-b]-[1,4]benzodiazepine-6-one), an M2 receptor selective antagonist, concentration-dependently (100-800 nmol/l) inhibited the decrease of tension development elicited by VNS. At the 100 ms vago-sympathetic impulse interval noradrenaline overflow was enhanced in the presence of AF-DX 116 400 and 800 nmol/l. However, already 100 nmol/l of the drug caused a maximum (fourfold) increase of acetylcholine overflow. It is concluded that acetylcholine released onto noradrenergic nerve fibres causes a small facilitation of noradrenaline overflow at a vago-sympathetic impulse interval of 100 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscarinic modulation of endogenous noradrenaline release from adrenergic terminals in the guinea‐pig colon

“…Muscarinic modulation of NA release has been demonstrated in a wide range of tissues, including heart and blood vessels (Muscholl, 1980;Vanhoutte & Levy, 1980), trachea (Racke , BaÈ hting, Brunn, Elsner & Wessler, 1991, iris (Bognar, Pallas, Fuder & Muscholl, 1988), vas deferens (Grimm et al, 1994), stomach (Yokotani & Osumi, 1993) and ileum (Alberts & StjaÈ rne, 1982). In particular, muscarinic facilitation of NA release through M 1 receptors has been reported in guinea-pig carotid arteries (Casado, Marin & Salaices, 1992;Casado, Sevilla, Alonso, MarõÁ n & Salaices, 1994) and in mouse (Costa & Majewski, 1991;Costa, Barrington & Jajewski, 1993) and rabbit atria (Habermeier-Muth, Altes, Forsyth & Muscholl, 1990).…”

Heterogeneity of presynaptic muscarinic receptors mediating inhibition of sympathetic transmitter release: a study with M2‐ and M4‐receptor‐deficient mice

“…It is well known that these receptors can mediate inhibition as well as facilitation of noradrenaline release (Fuder & Muscholl, 1995). The release‐facilitating receptors are likely to represent M 1 receptors across tissues and species (Muscholl et al ., 1989; Vizi et al ., 1989; Habermeier‐Muth et al ., 1990; Costa & Majewski, 1991; Casado et al ., 1992; Somogyi et al ., 1996). In contrast, the majority of release‐inhibiting receptors were suggested to be M 2 .…”

Relationship between pulse interval and respiratory sinus arrhythmia: a time- and frequency-domain analysis of the effects of atropine

“…This pre-treatment also limited the interaction of atropine with sympathetic nerve activity [17,31]. However betaadrenergic blockade may facilitate vagal tone [25,42,43].…”