An inhibition of post‐ganglionic motor transmission in the mammalian vas deferens by D‐lysergic acid diethylamide

Abstract

SUMMARY1. Under certain conditions D-lysergic acid diethylamide (LSD), 10-9-10 g/ml., exerted an immediate, prolonged and slowly reversible inhibitory effect upon the post-ganglionic motor transmission in desheathed guinea-pig vas deferens preparations.2. The most critical factor influencing this action of LSD appeared to be the train length. With short trains of less than 4 or 5 pulses the twitch inhibition produced by LSD was often total. With longer trains (5-20 pulses), the degree of inhibition declined with increase in train length.These results suggest the existence of two components in the motor response to post-ganglionic stimulation, distinguished by their susceptibility to LSD.3. The inhibition of the LSD-susceptible component was related to the dose of LSD in the range 10-9-10 g/ml., reaching a maximum at 0*5-1 x 10 g/ml. The response remnants elicited by trains of more than 5 pulses under these conditions could not be reduced further by a ten-to twenty-fold increase in LSD concentration to 10-5 g/ml. and were in fact slightly potentiated.4. The inhibition of post-ganglionic motor transmission by LSD was not explicable on the basis of an a-adrenoceptor blockade because it was not associated with any reduction in motor responses to noradrenaline.5. The use of propranolol excluded mediation of the LSD-inhibition by ,8-adrenoceptors.6. The LSD effect was not due to a non-specific smooth muscle depression because it was not associated with any reduction in motor responses to acetylcholine, ATP or bradykinin.7. The inhibitory effect of LSD on post-ganglionic transmission resembled that of noradrenaline in that it-was antagonized by phentolamine; N. AMBACHE AND OTHERS another a-adrenoceptor blocking agent, phenoxybenzamine, was less effective than phentolamine in this respect.8. The LSD-inhibition was obtained in preparations taken from reserpinized guinea-pigs.9. The inhibition of motor transmission in the vas deferens by LSD was confirmed in rats, Meriones shawii and rabbits.10. The inhibition of post-ganglionic transmission by LSD was unrelated to its ability to antagonize 5-hydroxytryptamine (5-HT), to which the longitudinal muscle of the guinea-pig vas deferens is insensitive. The more potent 5-HT antagonists, methysergide and BOL 148 were either virtually inactive or considerably weaker than LSD.

Inhibition of noradrenaline release by lysergic acid diethylamide

“…Discussion.-These results confirm and extend those of Ambache et al (1971) and Ambache, Dunk, Verney & Aboo Zar (1973); however, these workers consider that the motor innervation of the vas is non-adrenergic. The present results support the classical concept that noradrenaline is the motor transmitter in the vas deferens.…”

Adrenergic and 'non‐adrenergic' components in the contractile response of the vas deferens to a single indirect stimulus.

“…This relatively simple explanation of the origin of the first and second components of the response to a single pulse is at odds with at least two well established observations in the literature from experiments involving repetitive stimulation in rat vasa. First, reserpine or LSD, which in the present experiments reduced only the second component of the response to a single stimulus, are known to reduce the twitch or first component of the response to repetitive stimulation Ambache, Dunk, Verney & Zar, 1973;Hughes, 1973;McGrath, 1973;Gillespie & McGrath, 1974, 1975. Secondly, guanethidine, an adrenergic neurone blocking drug and which is known to block both components of the response to repetitive stimulation (Anton et al 1977), did not abolish the response to a single stimulus.…”

Pharmacological Characterization of the Presynaptic Α‐adrenoceptors Regulating Cholinergic Activity in the Guinea‐pig Ileum

“…It has been shown to be a potent agonist at presynaptic a2-adrenoceptors in the rat heart (Drew, 1976), rat vas deferens (Ambache, Dunk, Verney & Zar, 1973;Hughes, 1973), rat anococcygeus muscle and dog retractor penis muscle (Ambache, Killick, Srinivasan & Zar, 1975), but a weak agonist, or even an antagonist, at postsynaptic a1-adrenoceptors (Ambache et al, 1975;Drew, 1976). Hughes (1973) has reported that LSD inhibits the twitch response of the guinea-pig ileum by a presynaptic agonist action, which suggests that a2-adrenoceptors are involved.…”