Stimulatory Effect of Tolazoline on Smooth Muscle

Dzoljic, M.R.

doi:10.1111/j.1476-5381.1967.tb02126.x

Cited by 3 publications

(2 citation statements)

References 18 publications

(18 reference statements)

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“…The initial, and still the basic, observation supporting the presence of both receptors was that inhibition of tone in the canine ileum by adrenaline or NA could be blocked only if both at and ft blocking agents were simultaneously present (Ahlquist & Levy, 1959). This requirement has been confirmed in other species and in other sites including the colon (Furchgott, 1960;Bucknell & Whitney, 1964;Brody & Diamond, 1967;Dzoljic, 1967;Antonio, 1968;Day & Warren, 1968). In some of these experiments inhibition of the response to transmural stimulation rather than myogenic tone was studied bringing with it the possibility of an additional a site of inhibition on nerves.…”

Section: Discussionmentioning

confidence: 73%

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

Gillespie

Khoyi

1977

The Journal of Physiology

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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.

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Section: Discussionmentioning

confidence: 73%

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

Gillespie

Khoyi

1977

The Journal of Physiology

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“…Slope (95% confidence limits) minals during transmural stimulation. This seems unlikely, however, because the effects of the antagonists on the twitch did not correlate with their abilities to antagonize responses to clonidine, and because Dzoljic (1967) found that the potentiating effect of tolazoline persisted in preparations removed from reserpine-treated animals. He attributed the potentiation to an anticholinesterase action, which might be valid for tolazoline but is unlikely to hold for the other agonists since their potentiating effects were apparent at concentrations below those required to inhibit significantly cholinesterase activity (Boyd, Chang & Rand, 1960).…”

Section: Discussionmentioning

confidence: 98%

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

Drew

1978

British J Pharmacology

236

113

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1 The presynaptic ax-adrenoceptors located on the terminals of the cholinergic nerves of the guineapig myenteric plexus have been characterized according to their sensitivities to a-adrenoceptor agonists and antagonists. 2 Electrical stimulation of the cholinergic nerves supplying the longitudinal muscle of the guinea-pig ileum caused a twitch response. Clonidine caused a concentration-dependent inhibition of the twitch response; the maximum inhibition obtained was 80 to 95% of the twitch response. Oxymetazoline and xylazine were qualitatively similar to clonidine but were about 5 times less potent. Phenylephrine and methoxamine also inhibited the twitch response but were at least 10,000 times less potent than clonidine. 3 The twitch-inhibitory effects of clonidine, oxymetazoline and xylazine, but not those of phenylephrine or methoxamine, were reversed by piperoxan (0.3 to 1.0 jg/ml).4 Lysergic acid diethylamide (LSD) inhibited the twitch response, but also increased the basal tone of the ileum. Mepyramine prevented the increase in tone but did not affect the inhibitory action of LSD. Piperoxan or phentolamine only partially antagonized the inhibitory effect of LSD. 5 Phentolamine, yohimbine, piperoxan and tolazoline were potent, competitive antagonists of the inhibitory effect of clonidine with pA2 values of 8.51, 7.78, 7.64 and 6.57 respectively. 6 Thymoxamine was a weak antagonist of clonidine; it also antagonized the twitch-inhibitory effect of morphine. Thus, its effect against clonidine is probably not mediated specifically at presynaptic a-adrenoceptors. 7 Labetalol, itself, depressed the twitch response but did not antagonize the inhibitory effect of clonidine on the residual twitch. 8 The results demonstrate that the presynaptic a-adrenoceptors in the guinea-pig ileum are of the same type as those located presynaptically in sympathetically innervated tissues. They are a2-adrenoceptors and are different from those located postsynaptically.

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Reversible depression of electrically-induced contractions of guinea pig longitudinal muscle by a reversible inhibitor of prostaglandin synthetase

Holsapple

Blake

Yiml

1979

Prostaglandins and Medicine

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Stimulatory Effect of Tolazoline on Smooth Muscle

Cited by 3 publications

References 18 publications

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

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

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

Reversible depression of electrically-induced contractions of guinea pig longitudinal muscle by a reversible inhibitor of prostaglandin synthetase

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