A presynaptic excitatory M1 muscarine receptor at postganglionic cardiac noradrenergic nerve fibres that is activated by endogenous acetylcholine.
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)
Habermeier-Muth
A
A
Pharmakologisches Institut der Universität Mainz, Federal Republic of Germany.
Altes
U
U
Forsyth
K M
KM
Muscholl
E
E
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D011930:Reaction Time / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects
D002250:Carbon Radioisotopes; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D000109:Acetylcholine; C048593:otenzepad; D009638:Norepinephrine