Pharmacology of pH effects on carotid body chemoreceptors in vitro.
1. The carotid body and the carotid nerve were removed from anaesthetized cats and placed in a small Perspex channel through which Locke solution (at various pH values and usually equilibrated with 50% O(2) in N(2)) was allowed to flow. The glomus was immersed in the flowing solution while the nerve was lifted into oil covering the saline. Sensory discharges were recorded from the nerve and their frequency was used as an index of receptor activity. At times, a small segment of carotid artery, containing pressoreceptor endings, was removed together with the glomus. In this case, pressoreceptor discharges were recorded from the nerve.2. The amplitude of either chemo- or pressoreceptor discharges was not changed by strong acid solutions. Acid decreased the frequency of the baroreceptor discharges only when pH fell to less than 4.0. Solutions at low pH increased the chemosensory discharge, but acid depressed the increased chemoreceptor discharge elicited by KCl. These experiments indicated that H(+) ions probably acted as membrane ;stabilizers' without depolarizing either the nerve fibres or endings.3. Acid solutions increased the action of acetylcholine chloride (AChCl) (100-200 mug) on chemoreceptors. This effect probably was due either to inactivation of tissue cholinesterase or to enhanced sensitivity of the sensory endings to ACh.4. Choline chloride (10(-3)M), which favours ACh synthesis, protected the preparation against decay during prolonged experimentation. Hemicholinium-3 (HC-3), which blocks ACh synthesis in low concentrations (10(-5)M), depressed the chemosensory response to acid and to hypoxia when such stimuli were applied repeatedly. This concentration of HC-3 did not change effects of applied ACh.5. Substances which affect ACh release markedly changed the chemoreceptor discharge increase induced by acidity and other forms of stimulation. In the absence of Ca(2+), acid, anoxia, and interruption of flow provoked receptor depression while receptor excitation induced by ACh and KCl persisted. All stimuli excited and showed increased effectiveness as the Ca(2+) concentration was raised, but their effects declined as Ca(2+) was increased above normal values. Mg(2+) ions depressed the chemoreceptor effects induced by all these stimuli. The action of Mg(2+) was not due entirely to nerve ending block. Morphine sulphate (which decreases ACh release in other structures) also depressed the receptor response to acid and flow interruption.6. Cholinergic blocking agents such as mecamylamine, hexamethonium, atropine, dihydro-beta-erithroidine (DHE), HC-3 (10(-4)M), choline and acetylcholine (in combination with choline) depressed the effects of acid and ACh on the chemoreceptors. The effect induced by interruption of flow was depressed only by mecamylamine and DHE.7. Agents which affect the fate of released ACh, such as acetylcholinesterase and eserine salicylate, did not affect clearly the response of chemoreceptors to acid.8. The results suggest that acid stimulates chemoreceptor fibres through an indirect mechanism, viz. through increased release and/or decreased destruction of a presynaptic transmitter from the glomus cell. This transmitter is probably ACh (see following paper, Eyzaguirre & Zapata, 1968).
D000109:Acetylcholine / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002344:Carotid Body / Q000187:drug effects*; D002415:Cats; D002628:Chemoreceptor Cells / Q000187:drug effects*; D002794:Choline / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology; D008274:Magnesium / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008722:Methods; D009020:Morphine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010477:Perfusion; D010830:Physostigmine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D013390:Succinylcholine / Q000494:pharmacology; D009435:Synaptic Transmission
D006584:Hexamethonium Compounds; D010276:Parasympatholytics; D008464:Mecamylamine; D009020:Morphine; D001285:Atropine; D010830:Physostigmine; D000110:Acetylcholinesterase; D008274:Magnesium; D013390:Succinylcholine; D002794:Choline; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium