Drug receptor sites in the rabbit saphenous nerve

1. The actions of acetylcholine, carbachol, methacholine, pilocarpine, nicotine, tetramethylammonium, 1,1-dimethyl-4-phenylpiperazinium, histamine, 5-hydroxytryptamine, angiotensin, bradykinin and potassium chloride were investigated on the sensory endings of the rabbit saphenous nerve.2. By means of specific antagonists the presence of separate receptor sites sensitive to acetylcholine, histamine, 5-hydroxytryptamine and bradykinin were demonstrated.3. The cholinoceptive receptors were shown to be predominantly nicotinic, but there was evidence of the existence of at least a small population of muscarinic receptors.4. Catecholamines of both alpha and beta types exhibited some stimulatory activity on administration. It is unlikely that this was due to either vasomotor effects or to any action involving the arrectores pilorum muscles.5. The alpha-receptor stimulants modified the response to acetylcholine in a biphasic way. There was a brief enhancement of effect followed by a more prolonged depression. beta-receptor stimulation only produced a prolonged enhancement of acetylcholine-evoked activity.6. The discharge generated by acetylcholine was augmented by anticholinesterases and blocked by ganglion blocking agents. None of these drugs in reasonable doses affected the response to stroking the fur. The results therefore support earlier evidence against a sensory cholinergic synaptic link.