Presynaptic nicotine receptors mediating a positive feed-back on transmitter release from the rat phrenic nerve.
The effects of 1,1-dimethyl-4-phenylpiperazinium (DMPP) and of nicotine receptor antagonists on [3H]acetylcholine release from the rat phrenic nerve preincubated with [3H]choline were investigated in the absence and presence of cholinesterase inhibitors (presynaptic effects). Additionally, the effects of hexamethonium and tubocurarine on the muscle contraction of the indirectly stimulated diaphragm were examined (postsynaptic effects). DMPP (1-30 microM) increased (76-92%), whereas hexamethonium (0.001-1 mM) and tubocurarine (1-10 microM) decreased (52-60%) the release of [3H]acetylcholine following a train of 100 pulses at 5 Hz. The release caused by a longer train (750 pulses at 5 Hz) was only slightly affected by DMPP and tubocurarine. In the presence of neostigmine (10 microM) neither tubocurarine nor DMPP significantly modulated the evoked [3H]acetylcholine release. High DMPP concentrations (10 and 30 microM) enhanced the evoked release only when the pretreatment interval was reduced from 15 min to 20 s. Tubocurarine and hexamethonium concentration-dependently inhibited the end-organ response. Hexamethonium was 250-fold more potent on presynaptic than on postsynaptic nicotine receptors. It is concluded that the motor nerve terminals are endowed with presynaptic nicotine receptors. These autoreceptors mediate a positive feed-back mechanism that can be triggered by previously released endogenous acetylcholine. Receptor desensitization can be produced by high agonist concentrations (endogenous or exogenous agonists) and is probably one mechanism to limit the autofacilitatory process. The presynaptic receptors appear to differ in their pharmacological properties from the postsynaptic receptors.
D000818:Animals; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D005246:Feedback; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000502:physiology*; D014403:Tubocurarine / Q000494:pharmacology
D006584:Hexamethonium Compounds; D018377:Neurotransmitter Agents; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide; D014403:Tubocurarine