The site and receptors responsible for the inhibition by sympathetic nerves of intestinal smooth muscle and its parasympathetic motor nerves

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Abstract
The effects of 3 inhibitory stimuli, sympathetic nerve stimulation, noradrenaline (NA) [norepinephrine] and isoprenaline were examined on 3 forms of motor activity in the rabbit colon, the response to pelvic (parasympathetic) nerve stimulation, acetylcholine (ACh) and spontaneous tone. The response to pelvic nerve stimulation was most effectively inhibited by sympathetic nerve stimulation, much less effectively by NA and hardly at all by isoprenaline. The sympathetic nerves could inhibit the pelvic response at frequencies of stimulation which do not affect spontaneous tone. The inhibitory effect of sympathetic stimulation, and of NA, on the pelvic response was reduced by phentolamine (5 .times. 10-6 M) and unaffected by propranolol (5 .times. 10-6 M), suggesting the effect was mediated via .alpha. receptors. The response to ACh was inhibited by all 3 stimuli equally. The inhibitory effect of sympathetic nerve stimulation and of isoprenaline was reduced by propranolol (5 .times. 10-6 M). The inhibitory effect of NA was also reduced by propranolol but to a lesser extent. Phentolamine (5 .times. 10-6 M) had a small effect in reducing the inhibitory effect of sympathetic nerve stimulation or of NA. This effect of phentolamine was lost if the participation of motor nerves in the response to ACh was excluded by either tetrodotoxin 10-7 g/ml or cold storage for 10-14 days. Inhibition of the ACh response may take place mainly at the muscle by activation of .beta. receptors, but ACh may have a small indirect stimulant action through motor nerves and this may be susceptible to inhibition through .alpha. receptors. All 3 stimuli were equally effective in lowering smooth muscle tone. This inhibitory effect of sympathetic nerve stimulation and of isoprenaline was reduced by propranolol (5 .times. 10-6 M) and unaffected by phentolamine (5 .times. 10-6 M). The inhibitory effect of NA was reduced by propranolol but again was less sensitive to block than the other 2 ihibitory stimuli. Phentolamine was without effect on the inhibitory action of NA and the combination of phentolamine with propranolol was no more effective than propranolol alone. NA liberated by sympathetic nerves and isoprenaline may inhibit myogenic tone in the smooth muscle by an action on .beta. receptors, but the action of NA added to the bath cannot be fully explained in this way.