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

Abstract

SUMMARY1. The effects of three inhibitory stimuli, sympathetic nerve stimulation, noradrenaline (NA) and isoprenaline have been examined on three forms of motor activity in the rabbit colon, the response to pelvic (parasympathetic) nerve stimulation, acetylcholine (ACh) and spontaneous tone.2. The response to pelvic nerve stimulation is most effectively inhibited by sympathetic nerve stimulation, much less effectively by NA and hardly at all by isoprenaline. The sympathetic nerves can 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 is reduced by phentolamine 5 x 10-6 M and unaffected by propranolol 5 x 10-6 M suggesting the effect is mediated via a receptors.3. The response to ACh is inhibited by all three stimuli equally. The inhibitory effect of sympathetic nerve stimulation and of isoprenaline is reduced by propranolol 5 x 10-6 M. The inhibitory effect of NA is also reduced by propranolol but to a lesser extent. Phentolamine 5 x 10-6 M has a small effect in reducing the inhibitory effect of sympathetic nerve stimulation or of NA. This effect of phentolamine is lost if the participation of motor nerves in the response to ACh is excluded by either tetrodotoxin 10-7 g/ml. or cold storage for 10-14 days. These results suggest that inhibition of the ACh response takes place mainly at the muscle by activation of /8 receptors but that ACh may have a small indirect stimulant action through motor nerves and this is susceptible to inhibition through a receptors.4. All three stimuli are equally effective in lowering smooth muscle tone. This inhibitory effect of sympathetic nerve stimulation and of isoprenaline * Present address: Department of Pharmacology, University of Tehran, Tehran 14, Iran.J. S. GILLESPIE AND M. A. KHOYI is reduced by propranolol 5 x 106M and unaffected by phentolamine 5 x 106 M. The inhibitory effect of NA is reduced by propranolol but again is less sensitive to block than the other two inhibitory stimuli. Phentolamine is without effect on the inhibitory action of NA and the combination of phentolamine with propranolol is no more effective than propranolol alone. These results suggest that NA liberated by sympathetic nerves and isoprenalins inhibit myogenic tone in the smooth muscle by an action on fi receptors but the action of NA added to the bath cannot be fully explained in this way.

Stimulation of lumbar sympathetic nerves evokes contractions of cat colon circular muscle mediated by ATP and noradrenaline

“…Acute transection of them enhances basal intraluminal pressures and the amplitude of spontaneous contractions, indicating a tonic inhibitory action (de Groat & Krier, 1979). Conversely, electrical stimulation of LCN decreases basal intraluminal pressure and amplitude of cholinergic (pelvic nerve-evoked) contractions (Gillespie & McKenna, 1961;de Groat & Krier, 1976;Gillespie & Khoyi, 1977). These inhibitory effects on colonic smooth muscle are mediated through prejunctionala-I Author for correspondence.…”

Evidence for the existence of ‘atypical’β‐adrenoceptors (β3‐adrenoceptors) mediating relaxation in the rat distal colon in vitro

“…Responses to noradrenaline and isoprenaline which are resistant to blockade of classical a-and fl-adrenoceptors have been reported in a number of animal isolated tissues, such as guinea-pig ileum (Wikberg, 1977;Bond et al, 1986;Bond & Clarke, 1987); rabbit stomach (Bristow et al, 1970); rabbit colon (Gillespie & Khoyi, 1977); dog colon (Grivegnee et al, 1984); rat gastric fundus (Dettmar et al, 1986b;Kelly & MacDonald, 1990) and guinea-pig gastric fundus (Coleman et al, 1987). So-called 'atypical',B-adrenoceptors mediating lipolysis in rat adipocytes are also resistant to blockade by classical fi-adrenoceptor antagonists (Stanton, 1972;Harms et al, 1977) and in addition are characterized by the high selectivity and potency of a novel group of agonists Wilson et al, 1984).…”

Characterization of catecholamine‐mediated relaxations in rat isolated gastric fundus: evidence for an atypical β‐adrenoceptor

“…However, relaxant responses to catecholamines which are resistant to blockade by a-and f-adrenoceptor antagonists have also been reported in a number of gastrointestinal smooth muscle preparations including rabbit stomach (Bristow et al, 1970), rabbit colon (Gillespie & Khoyi, 1977), rat oesophageal smooth muscle (Buckner & Christopherson, 1974), guinea-pig ileum (Wikberg, 1977;Bond et al, 1986;Bond & Clarke, 1987), dog colon (Grivegnee et al, 1984), rat gastric fundus (Dettmar et al, 1986;McLaughlin & MacDonald, 1990a;, rat proximal colon (Croci et al, 1988;Manara et al, 1989;Bianchetti & Manara, 1990), rabbit jejunum (Norman & Leathard, 1990), rat jejunum (Van der Vliet et al, 1990) and rat distal colon (McLaughlin & MacDonald, 1989;1990b). In the guinea-pig ileum, the order and relative potency of catecholamines is consistent with /3-adrenoceptors although responses were resistant to propranolol (Bond & Clarke, 1988).…”