Presence of acetylcholine and transmitter release from carotid body chemoreceptors.

Abstract

The evidence presented in the preceding three papers indicates that in all probability the carotid body chemoreceptors form a sensory synapse with a presynaptic element (presumably the glomus cells) and a postsynaptic element, namely, the sensory nerve endings (cf. also de Castro, 1951). The preceding studies also indicate that chemoreceptor impulses may be elicited by a substance (or substances) released from glomus tissues during stimulation. These agents have been tentatively designated as 'generator' or 'transmitter' substances. During some forms of stimulation (induced by hypoxia, hypercapnia and electrical stimulation) release of acetylcholine (ACh) or a similar substance seems to be responsible for the initiation of the chemosensory discharge. During stimulation induced by receptor exposure to N2, to NaCN or by interruption of flow, chemicals other than ACh may be released as well (Eyzaguirre & Koyano, 1965a,b,c).In order to establish the existence of chemical generation of sensory impulses it is important to know: (i) the nature and content of possible transmitter substances in carotid body tissues; (ii) whether or not such substances are released during stimulation and whether these activate sensory nerve endings. These problems were partly resolved in the present study. In the first place, ACh was found in carotid body tissues in sufficient quantities to be considered as a possible chemical transmitter during certain forms of stimulation. Secondly, chemicals were released by either electrical or 'natural' stimulation and these substances activated another chemoreceptor preparation placed in series. The nature of the released agent(s) remained undetermined.

The districution of biogenic amines in the carotid bifurcation region

“…The absence of an intense fluorescence in ungassed control sections of normal carotid bodies distinguishes the condensation product from tissue autofluorescence, and the persistence of the glomus cell fluorescence 3 weeks after superior cervical ganglionectomy suggests independence of the glomus cell amine from that in sympathetic nerves. At the reaction time used (1 hr) the formaldehyde condensation method has a high specificity for noradrenaline, dopamine and 5-hydroxytryptamine but not adrenaline (Corrodi & Hillarp, 1963, 1964 Eyzaguirre et al (1965) isolated an acetylcholine-like substance from the carotid body, and cholinesterases are known to be present in this organ though there is disagreement as to their precise localization (see Hollinshead & Sawyer, 1945;Koele, 1951;Ross, 1957;Biscoe & Silver, 1966). Whether it is acetylcholine or the phenolic amine(s) which initiate the chemoreceptor impulse, or whether these agents subserve some quite different function within the carotid body, awaits clarification.…”

“…Lever, Lewis & Boyd (1959) found electron microscopical and histochemical evidence for the presence of phenolic amines in carotid body glomus cells (see also Rahn, 1961), but recently Eyzaguirre, Koyano & Taylor (1965) have extracted an acetylcholine-like substance in large amounts from the carotid body of the cat.…”

Pharmacology of pH effects on carotid body chemoreceptors in vitro

“…Such a mechanism would entail the release of a transmitter or generator substance from the glomus tissue (presumably the glomus cells) which would activate the sensory nerve terminals. That a chemical is released from carotid body tissues is suggested by Loewi-type experiments where in vitro it is possible to increase the chemosensory discharge of a downstream preparation by stimulation of an upstream organ (Eyzaguirre et al 1965). Also, it is possible to obtain functional innervation of the chemoreceptors by fibres from the laryngeal nerve, which normally do not respond to changes in the composition of the blood (Eyzaguirre & Zapata, 1967 Eyzaguirre et al 1965); (ii) choline, which is the 583 C. EYZAGUIRRE AND P. ZAPATA substrate for ACh synthesis, protects the chemoreceptor preparation against deterioration during prolonged experiments in vitro.…”

“…To examine these alternatives, experiments were conducted to test direct effects of acid on carotid nerve and effects of pharmacological agents on the response of chemoreceptors to acid. Most of the substances selected for this study were known either to favour or to antagonize cholinergic transmission in other systems, since earlier studies indicated that a cholinergic mechanism was probably important in the origin of sensory discharges, evoked by either low Po2, high Pco2 or electrical stimulation (Eyzaguirre & Koyano, 1965a-c;Eyzaguirre, Koyano & Taylor, 1965; see also Eyzaguirre & Zapata, 1967, 1968.…”

The release of acetylcholine from carotid body tissues. Further study on the effects of acetylcholine and cholinergic blocking agents on the chemosensory discharge

“…EYZAGUIRRE AND P. ZAPATA Evidence has been presented elsewhere which indicates that the sensory terminations are probably activated indirectly by different stimulating agents such as low Po2, high PcO2, acidity or electrical currents (Eyzaguirre & Koyano, 1965a, b, c; Ezyaguirre & Zapata, , 1968. In fact, activation of the nerve terminals seems to be accomplished by a chemical released from the glomus tissue (Eyzaguirre, Koyano & Taylor, 1965). The nature of this intermediary substance has remained uncertain, although indirect evidence indicates that it may be acetylcholine (see .…”