Effect of synaptic transmission blockade on morphine action in the guinea-pig myenteric plexus.
Morphine, which inhibits release of acetylcholine from neurons in the myenteric plexus, also inhibits the spontaneous electrical activity of some myenteric neurons. To determine whether morphine acts at a site presynaptic to these neurons, we investigated this morphine effect under conditions of synaptic transmission blockade. Synaptically driven action potentials evoked by point stimulation were recorded extracellularly, and it was shown that all synaptic responses were eliminated or greatly reduced in Ca-free, high-Mg Ringer's with ethylenebis [(oxyethylenenitrilo)]-tetraacetic acid (EGTA), suggesting that synaptic transmission was blocked. Under these conditions, the ability of morphine to inhibit spontaneous electrical activity was virtually unimpaired. Assuming a single locus of narcotic action in the myenteric plexus, it is unlikely, therefore, that the primary action of opiates is to stimulate release of an inhibitory transmitter, to prevent release of an excitatory transmitter or to block the postsynaptic receptor for an excitatory transmitter. Rather, opiates may raise the membrane threshold of a class of neurons. Electric field stimulation activates myenteric neurons, resulting in a morphine-sensitive release of acetylcholine and a contraction of the longitudinal muscle. The ability of field stimulation to induce contractions and of morphine to inhibit these contractions, was virtually unchanged when the only two known excitatory inputs to the cholinergic motor neuron were eliminated by receptor blockade. These observations, taken together, suggest that opiates act directly on the cholinergic motor neuron of the myenteric plexus.
D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000502:physiology*; D009538:Nicotine / Q000502:physiology; D011955:Receptors, Drug / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D013997:Time Factors
D011955:Receptors, Drug; D012701:Serotonin; D009538:Nicotine; D009020:Morphine