Inhibition Of Stimulation-induced Contractions Research Articles

Some pharmacological studies of venom from the inland taipan ( Oxyuranus microlepidotus)

The present study was designed to obtain a basic pharmacological profile of venom from the inland taipan ( Oxyuranus microlepidotus). Venom (0.05–50 μg/ml) produced dose-dependent contractions in guinea-pig ileum, which could not be reproduced upon second administration. The cyclooxygenase inhibitor indomethacin (1 μM), a preceding anaphylactic response induced by egg albumin and inactivation of phospholipase A 2 (PLA 2) by incubation with 4-bromophenacyl bromide (1.8 mM) all significantly inhibited responses to venom (0.5 μg/ml). Venom (0.5 μg/ml) caused inhibition of stimulation-induced contractions in the prostatic segment of rat vas deferens which was not significantly affected by the α 2-adrenoceptor antagonist idazoxan (0.3 μM). Venom (10 μg/ml) caused time-dependent inhibition of the rat electrically stimulated phrenic nerve–diaphragm preparation, positive inotropic and chronotropic responses in rat isolated atria and relaxation in rat endothelium-denuded and -intact isolated aortae. In endothelium-intact aortae, the nitric oxide synthase inhibitor N-nitro- l-arginine (NOLA, 0.1 mM) significantly inhibited the response to venom (10 μg/ml). Venom (50 μg/kg, i.v.) caused an immediate drop in blood pressure followed by cardiovascular collapse in anaesthetised rats. Venom (10 μg/kg, i.v.) caused a gradual fall in blood pressure which was sometimes accompanied by a temporary cessation of respiration. A PLA 2 assay detected the presence of PLA 2 in the venom. These results suggest that the venom contains a component capable of causing the synthesis of arachidonic acid metabolites and a component capable of relaxing vascular smooth muscle. The inhibitory effect on the phrenic nerve–diaphragm is probably due to the previously identified neurotoxin (paradoxin).

Dual effects of capsaicin on responses of the rabbit ear artery to field stimulation

1. The effects of capsaicin (Cap) on contractions of ring segments of rabbit ear artery induced by field stimulation were studied. 2. At low concentrations (0.3-3 microM) Cap caused transient enhancement and at higher concentrations (above 3 microM) inhibition of stimulation-induced contractions, without affecting noradrenaline (NA)-induced contractions. 3. In the continuous presence of high concentrations of Cap, rebound facilitation was observed after inhibition, and at this stage, Cap elicited less inhibition of the response. 4. Repeated application of Cap at 60 min intervals irreversibly desensitized the artery to the inhibitory effect of Cap. 5. Functional removal of the endothelium enhanced the facilitatory effect of low concentrations of Cap and attenuated its inhibitory effect. 6. Pretreatment with indomethacin abolished the facilitatory effect of Cap and enhanced its inhibitory effect, indicating that prostaglandins are involved in the action of Cap. The effect of indomethacin was more marked in preparations from which the endothelium had been removed. 7. Desensitization to substance P (SP) or substance K (SK), did not affect either the inhibitory or the facilitatory effect of Cap. 8. These results suggest that the dual effects of Cap on stimulation-induced contractions of rabbit ear artery may arise from the release of multiple mediators that act prejunctionally to modulate NA release. The stimulant effect seems to be mediated by prostanoids, while the inhibitory effect seems to be caused by a substance(s) that is not SP or SK. The possibility that the mediator is calcitonin gene-related peptide requires further study.