6533b86efe1ef96bd12cc05c
RESEARCH PRODUCT
Muscarine receptors on the rat phrenic nerve, evidence for positive and negative muscarinic feedback mechanisms.
M. MaiA. DienerIgnaz WesslerM. Karlsubject
medicine.medical_specialtyScopolamineMotor nerveStimulationIn Vitro Techniqueschemistry.chemical_compoundInternal medicineMuscarinic acetylcholine receptormedicineOxotremorineAnimalsPharmacologyMuscarineChemistryOxotremorineRats Inbred StrainsGeneral MedicineReceptors MuscarinicAcetylcholineElectric StimulationNeostigmineRatsPhrenic NerveEndocrinologymedicine.anatomical_structurePeripheral nervous systemPotassiumAcetylcholineScopolamine Hydrobromidemedicine.drugdescription
Neuronal transmitter stores of the rat phrenic nerve were labelled by incubation with [3H]choline. Release of [3H]acetylcholine was elicited by electrical nerve stimulation (100 or 1500 pulses, 5 or 25 Hz) or by high potassium (27 mmol/l) and the effects of the muscarine receptor agonist oxotremorine and the antagonist scopolamine were investigated. Neither oxotremorine nor scopolamine affected the basal tritium efflux. A low concentration of oxotremorine (10 nmol/l) enhanced and a high concentration of oxotremorine (1 μol/l) reduced the electrically evoked [3H]acetylcholine release. Likewise, the high potassium-evoked [3H]acetylcholine release was reduced by a high concentration of oxotremorine. Both effects of oxotremorine, increase and decrease, were abolished by a pretreatment (30 min before the first stimulation period) with 0.1 μmol/l scopolamine. Scopolamine (0.1 μol/l) alone, enhanced [3H]acetylcholine release evoked by 100 pulses (5 Hz) or by high potassium. Scopolamine, however, reduced [3H]acetylcholine release evoked by 1500 pulses (5 Hz or 25 Hz). The concentration-response curves obtained for scopolamine under these latter stimulation conditions were flat-running and biphasic which might indicate the involvement of two opposite effects (increase and decrease) of scopolamine under the present stimulation conditions. Both effects of scopolamine were reduced in the presence of 10 gmol/l neostigmine. It is concluded that muscarine receptors are present within the endplate region of motor nerves. Transmitter release from motor nerves appears to be regulated by two muscarinic feedback mechanisms. The negatively operating system is activated during short stimulation periods and the positively operating system becomes additionally apparent during long stimulation periods. Blockade of cholinesterase can hide presynaptic muscarinic mechanisms on motor nerves.
year | journal | country | edition | language |
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1987-06-01 | Naunyn-Schmiedeberg's archives of pharmacology |