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

Abstract

1. Both carotid bodies were removed from cats and placed in a small Perspex channel through which Locke solution was allowed to flow under a layer of paraffin oil. Stimulation of the upstream (‘donor’) organ elicited an increased sensory discharge in the downstream (‘detector’) preparation (Loewi effect). 2. This effect was enhanced by eserine, depressed by hexamethonium and blocked by either mecamylamine or acetylcholinesterase. The Loewi effect did not disappear when chronically denervated (4 days) ‘donor’ carotid bodies were stimulated. 3. These experiments led to the conclusion that ACh is released by the carotid body tissues (probably from the glomus cells) during stimulation and that this substance is responsible for the initiation of the chemosensory discharges. 4. In single preparations the chemosensory endings proved to be very sensitive to ACh especially in the presence of eserine which, in all probability, inactivated the tissue cholinesterase. Curarizing agents such as mecamylamine, hexamethonium, (+)‐tubocurarine and atropine blocked the response of the sensory endings to applied ACh in what appeared to be ‘surmountable’ antagonism.

Pharmacology of pH effects on carotid body chemoreceptors in vitro

“…Mecamylamine has been used as a ganglionic and neuromuscular blocking substance with success (Bennett, Tyler & Zaimis, 1957;Blackman & Ray, 1964;McIsaac & Millerschoen, 1963). We tried it on the 574 pH AND CAROTID CHEMORECEPTORS carotid body chemoreceptors because this secondary amine readily penetrates through membranes (Bennett et al 1957) and could be more effective than other quaternary ammonium compounds used in the past (Eyzaguirre & Koyano, 1965b; see also Eyzaguirre & Zapata, 1968).…”

“…This substance was used because it depresses the chemoreceptor 576 pH AND CAROTID CHEMORECEPTORS response to hypoxia and hypercapnia (Eyzaguirre & Koyano, 1965b) as well as that elicited by ACh (Eyzaguirre & Zapata, 1968).…”

“…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.…”

Presynaptic regulation of isolated neonatal rat carotid body type I cells by histamine

“…ACh and ATP -Acetylcholine and the co-release of ATP Acetylcholine (ACh), already known to be an excitatory neurotransmitter released from the pre-synaptic terminals of motor neurons, has been linked to play an excitatory role in the modulation of breathing within the carotid body (Eyzaguirre & Zapata, 1968;Gonzalez et al, 1994). ATP, a molecule used for energy, has also been shown to exhibit abilities as an extracellular signaling molecule within the central nervous system (Burnstock, 1997).…”

Ventilatory stimulation by dopamine‐receptor antagonists in the mouse

“…Since a-receptors have been proposed as the site of action of dopamine in the carotid body (Sampson, 1972), and muscarinic receptors can influence chemosensory activity (Eyzaguirre & Zapata, 1968), we wished to obtain clearer evidence that the ventilatory effects of drugs used as dopamineantagonists were due principally to their action at dopamine-receptors. Therefore, we studied the ventilatory effects of a group of dopamine-receptor blocking drugs that are discordant in their effects at other receptor classes potentially involved in ventilatory control.…”