Alpha-adrenoceptor mediated facilitation of acetylcholine release in the rat perfused heart.
Rat hearts were isolated with the vagus nerves intact and perfused, and the neuronal acetylcholine stores were pulse labeled with [14C]choline. The overflow of [14C]choline/acetylcholine evoked by extrinsic vagus nerve stimulation (3 Hz and 720 pulses or 10 Hz and 1200 pulses) was determined by liquid scintillation spectrometry and used as a measure for acetylcholine release. The postjunctional changes in atrial contraction and beating frequency were also recorded. Compared to controls, oxymetazoline and xylometazoline [but not clonidine, (3,4-dihydroxyphenyl-amino)-2-imidazoline), methoxamine and norepinephrine] enhanced the evoked overflow of 14C-activity in a concentration-dependent manner without changing the ratio between choline and acetylcholine determined by paper chromatography. Norepinephrine (10 mumol/l) inhibited the evoked overflow in the presence of propranolol plus yohimbine. The oxyme-tazoline-induced increase in evoked overflow was unaffected by rauwolscine (1 mumol/l), idazoxan (0.3 and 5 mumol/l), and yohimbine (0.3 and 5 mumol/l), but significantly reduced by phentolamine (5 mumol/l), prazosin (0.03 mumol/l), the (-)-enantiomer of WB 4101 (0.1 mumol/l) and SK&F 104078 (3 mumol/l). The overflow of 14C-activity evoked by field stimulation was increased by oxymetazoline the absence and presence of hemicholinium-3. The results are compatible with an alpha-1 adrenoceptor-mediated facilitation of exocytotic acetylcholine release from the rat heart in vitro. The increase in evoked neurotransmitter overflow, however, was not accompanied by an increase in postjunctional heart responses to vagus stimulation due to nonselective blocking properties of the facilitating agonists.
Bognar
I T
IT
Pharmakologisches Institut, Universität Mainz, Federal Republic of Germany, West.
Baretti
R
R
Fischer
S
S
Veldet
C
C
Fuder
H
H
D000109:Acetylcholine / Q000032:analysis / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D002794:Choline / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D048288:Imidazolines; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009431:Neural Conduction / Q000187:drug effects*; D010109:Oxymetazoline / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014630:Vagus Nerve
D000316:Adrenergic alpha-Agonists; D002395:Catecholamines; D015259:Dopamine Agents; D007093:Imidazoles; D048288:Imidazolines; D011942:Receptors, Adrenergic, alpha; D010109:Oxymetazoline; C011775:(3,4-dihydroxyphenylamino)-2-imidazoline; D002794:Choline; D000109:Acetylcholine; C009695:xylometazoline