The Effects of Drugs on Neurotransmission in the Vas Deferens

1) The aim of this study was to investigate the effects of field stimulation and drugs on neurotransmission in the vas deferens. 2) Field stimulation of mouse isolated vasa resulted in biphasic motor responses that were abolished by tetrodotoxin (TTX). The initial component of this response was selectively inhibited by morphine and clonidine. The second component was inhibited by phentolamine. 3) After 6-hydroxydopamine (6-OHDA) pretreatment, field stimulation produced a small, monophasic contraction, which was unaffected by phentolamine and by TTX. Vasa from 6-OHDA pretreated mice were supersensitive to noradrenaline (NA). 4) In control anaesthetised rats, motor responses of the in situ vas to field stimulation or to spinal nerve stimulation were biphasic and were abolished by TTX. After 6-OHDA pretreatment, in situ field stimulation produced monophasic contractions that were resistant to TTX, suggesting that these responses may be non-neuronal, resulting from direct stimulation of supersensitive smooth muscle. 5) Morphine and clonidine potentiated the second noradrenergic component of the biphasic motor response to field stimulation at a time when the overflow of radioactivity from vasa preincubated with (3H)-NA was increased. 6) The ability of morphine and clonidine to potentiate the field stimulation-induced overflow of radioactivity occurred in the presence of a combination of drugs which block the removal mechanisms for NA. 7) NA and electrical field stimulation increased phosphoinositide hydrolysis, reflected in [32P]-phosphatidic acid (PA) formation in the mouse vas deferens and these responses were blocked by prazosin and by TTX. 8) Neither morphine nor clonidine affected basal levels of [32P]-PA formation or the ability of NA to enhance [32P]-PA formation but both drugs potentiated the ability of field stimulation to increase the formation of [32P]-PA. This suggests that these drugs enhance the field stimulation-induced release of NA in the mouse vas deferens. A possible explanation for the findings that morphine and clonidine apparently inhibit release of one co-transmitter whilst potentiating the release of another is discussed. 9) Part of the study investigated the effects of chronically treating mice with thyroxine (T4). The level of T4 in the serum was increased in mice pretreated with T4, and this was accompanied by changes in pre- and post-synaptic receptor sensitivity. 10) Pretreatment with T4 produced a presynaptic subsensitivity to morphine and clonidine and a postsynaptic subsensitivity to NA and carbachol. In these animals, the ability of morphine and clonidine to potentiate the overflow of (3H)-NA was diminished. A possible explanation for these observations is considered