Stimulation of alpha 1-adrenoceptors increases electrically evoked [3H]acetylcholine release from the rat phrenic nerve.
The modulation by sympathomimetic amines of the electrically evoked [3H]acetylcholine release from the motor nerve was investigated. Phenylephrine (10 mumol/l), alpha-methylnoradrenaline (10 mumol/l) and adrenaline (1 mumol/l) enhanced the electrically evoked [3H]acetylcholine release from the rat phrenic nerve. The enhancing effect of phenylephrine was completely prevented by low concentrations of prazosin (0.1 or 0.01 mumol/l) whereas a high concentration of yohimbine (1 mumol/l) was necessary to abolish the effect of phenylephrine. The simultaneous blockade of alpha- and beta-adrenoceptors, i.e. propranolol (0.1 mumol/l) together with prazosin (0.01 mumol/l) or yohimbine (1 mumol/l), was required to abolish the enhancing effect of alpha-methylnoradrenaline. Likewise, the enhancing effect of adrenaline could be abolished only by a combination of two antagonists (propranolol together with yohimbine or prazosin). Neither clonidine nor oxymetazoline (1 or 10 mumol/l) modulated the evoked [3H]acetylcholine release. The experiments showed the existence of alpha-adrenoceptors which are present on the motor nerve and whose stimulation mediates an increase in evoked transmitter release. The different potencies found for prazosin and yohimbine indicate that an alpha 1-subtype of the receptors was involved. Increased sympathetic activity may facilitate neuromuscular transmission by stimulation of presynaptic alpha- and beta-adrenoceptors.
Wessler
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Department of Pharmacology, University of Mainz, F.R.G.
Ladwein
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Szrama
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E
D000109:Acetylcholine / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010109:Oxymetazoline / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D010656:Phenylephrine; D015016:Yohimbine; D010109:Oxymetazoline; D011433:Propranolol; D003000:Clonidine; D000109:Acetylcholine; D011224:Prazosin