Stimulation of beta 1-adrenoceptors enhances electrically evoked [3H]-acetylcholine release from rat phrenic nerve.
1. The effects of isoprenaline, noradrenaline and fenoterol on the electrically evoked release of [3H]-acetylcholine from the rat phrenic nerve were investigated. 2. Isoprenaline (0.1 mumol/L) and noradrenaline (1 mumol/L) enhanced evoked [3H]-acetylcholine release by about 90%, an effect which was abolished by CGP 20712A (0.1 mumol/L), a specific antagonist at beta 1-adrenoceptors. Noradrenaline still enhanced [3H]-acetylcholine release in the presence of phentolamine (1 mumol/L). 3. The enhancing effect of both isoprenaline and noradrenaline decreased at prolonged exposure times (24-32 min). A pre-exposure of the tissue to a low concentration (0.01 mumol/L) of isoprenaline prevented the enhancing effect of 0.1 mumol/L isoprenaline. 4. Fenoterol, a specific agonist at beta 2-adrenoceptors, did not modify evoked [3H]-acetylcholine release. 5. The present results indicate the existence of facilitatory beta 1-adrenoceptors on the motor nerve. These receptors appear to be desensitized either by a high concentration of, or by a long exposure to, agonists. Under the present conditions noradrenaline enhances the release of newly synthesized transmitter mainly by stimulation of beta-adrenoceptors.
Wessler
I
I
Department of Pharmacology, University of Mainz, FRG.
Holzer
G
G
Künster
A
A
D000109:Acetylcholine / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D005280:Fenoterol / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D005280:Fenoterol; D011433:Propranolol; C049763:CGP 20712A; D007545:Isoproterenol; D000109:Acetylcholine; D009638:Norepinephrine; D010646:Phentolamine