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Calcitonin-induced analgesia and calcium depletion in mice
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MODULATION OF PAIN. I. Haulicx, C. Neamfu, G. Petrescu, D. Brinigteanu, S. Sla'tineanuand Kamal Ameis, Department of Physiology, Institute of Medicine and Pharmacy, IaSi-Romania.
ANGIOTENSIN
The flick tail test was used in order to measure the thermoalgesic sensitivity in wake rats with a counting thermoalgesimeterbuilt by us. The intracerebroventricular(i.c.v.) administrationof Ang I and Ang II solution in physiological saline into the IIIrd ventricle resulted in biphasic, dose-dependenteffects. While small doses (0.5-5 ng/ml saline) decreased the latency time, high doses (up to 100 ng/ml saline) significantly increased it. Both effects were of a short duration (4-6 min.) and blocked by saralasin. In the presence of naloxone, only the latency time increases obtained with high amounts of Ang II were suppressed. Parachlorphenylalanine (PCPA) and ketanserin did not influence the angiotensins induced effects. I.c.v. infusion of pure angiotensinogen (Sigma) determined similar dose-dependent biphasic effects. Purified hog renin (Sigma) injected i.c.v. resulted only in a significant increase of the latency time which was blocked by saralasin. The obtained results seem to demonstrate that the thermoalgesic sensitivity of rats is influenced both by exogenous Ang I and II as well as by the endogenous cerebral angiotensins. In agreement with previous data showing the analgesic properties of captopril (Stein et al., 1980) and opiate releasing actions of Ang II (Beuers system participation in the et al., 1982), the cerebral renin-angiotensin modulation of pain sensitivity is discussed. In small, physiological concentrations the angiotensins behave like anti-opioid hyperergic agents while in pharmacological amounts the indirect, analgesic effects prevail in relation with a possible increase of the enkephalin content as a consequence of the conversion enzyme (enkephalinase II) inhibition through excessive substrate amounts. CALCITONIN-INDUCED ANALGESIA AND CALCIUM DEPLETION IN MICE. P. GIUSTI, M. Carrara, S. Zampiron and L. Cima, Department of Pharmacology, University of Padua, 35131 Padua, Italy. Aim of Investigation: It is reported that the whole brain and synaptosomal calcium levels are decreased after the administration of analgesic narcotics. Consistently, an increase of calcium in the brain, obtained by Ca2+ i.c.v. in mice or rats,ewokes hyperalgesia together with hyperphagia and thirst, gastric acid hypersecretion, hypothermia and hypoactivity. All these effects are opposite in comparison with those showed by calcitonin (CT) i.c.v. The present study examines the relation between the whole brain calcium level and the analgesic effect after the central administration of CT in mice. Methods: The hot plate test was performed at 55+0.5OC in the mice treated i.c.v. with 7.5 U/kg of salmon-CT. The whole brain calcium was detected directly by atomic absorption. Results: After CT administration a rapidly increasing and persistent (more than 6h) analgesia was observed. Almost specularly the whole brain calcium showed a prompt and long-lasting depletion of the ion and its minimum level (about -40%) was in connection with the minimum peak of analgesia (after 10 min). Conclusions: CT analgesia has been showed to be correlated with calcium depletion in brain, like that induced by opiate. This ion-depletSon-effect is common to some depressant drugs such as ethanol and reserpine, but not barbiturate. Therefore, CT which possesses intrinsic analgesic activity unaffected by naloxone and devoid of cross-tolerance to morphine, may funct ion as endogenous modulator of opiate action through modulation of cellular Ca2+ level in the CNS. It appears therefore that calcium plays a critical role in the mechanism of action of opiate and non opiate systems.
MODULATION OF PAIN. I. Haulicx, C. Neamfu, G. Petrescu, D. Brinigteanu, S. Sla'tineanuand Kamal Ameis, Department of Physiology, Institute of Medicine and Pharmacy, IaSi-Romania.
ANGIOTENSIN
The flick tail test was used in order to measure the thermoalgesic sensitivity in wake rats with a counting thermoalgesimeterbuilt by us. The intracerebroventricular(i.c.v.) administrationof Ang I and Ang II solution in physiological saline into the IIIrd ventricle resulted in biphasic, dose-dependenteffects. While small doses (0.5-5 ng/ml saline) decreased the latency time, high doses (up to 100 ng/ml saline) significantly increased it. Both effects were of a short duration (4-6 min.) and blocked by saralasin. In the presence of naloxone, only the latency time increases obtained with high amounts of Ang II were suppressed. Parachlorphenylalanine (PCPA) and ketanserin did not influence the angiotensins induced effects. I.c.v. infusion of pure angiotensinogen (Sigma) determined similar dose-dependent biphasic effects. Purified hog renin (Sigma) injected i.c.v. resulted only in a significant increase of the latency time which was blocked by saralasin. The obtained results seem to demonstrate that the thermoalgesic sensitivity of rats is influenced both by exogenous Ang I and II as well as by the endogenous cerebral angiotensins. In agreement with previous data showing the analgesic properties of captopril (Stein et al., 1980) and opiate releasing actions of Ang II (Beuers system participation in the et al., 1982), the cerebral renin-angiotensin modulation of pain sensitivity is discussed. In small, physiological concentrations the angiotensins behave like anti-opioid hyperergic agents while in pharmacological amounts the indirect, analgesic effects prevail in relation with a possible increase of the enkephalin content as a consequence of the conversion enzyme (enkephalinase II) inhibition through excessive substrate amounts. CALCITONIN-INDUCED ANALGESIA AND CALCIUM DEPLETION IN MICE. P. GIUSTI, M. Carrara, S. Zampiron and L. Cima, Department of Pharmacology, University of Padua, 35131 Padua, Italy. Aim of Investigation: It is reported that the whole brain and synaptosomal calcium levels are decreased after the administration of analgesic narcotics. Consistently, an increase of calcium in the brain, obtained by Ca2+ i.c.v. in mice or rats,ewokes hyperalgesia together with hyperphagia and thirst, gastric acid hypersecretion, hypothermia and hypoactivity. All these effects are opposite in comparison with those showed by calcitonin (CT) i.c.v. The present study examines the relation between the whole brain calcium level and the analgesic effect after the central administration of CT in mice. Methods: The hot plate test was performed at 55+0.5OC in the mice treated i.c.v. with 7.5 U/kg of salmon-CT. The whole brain calcium was detected directly by atomic absorption. Results: After CT administration a rapidly increasing and persistent (more than 6h) analgesia was observed. Almost specularly the whole brain calcium showed a prompt and long-lasting depletion of the ion and its minimum level (about -40%) was in connection with the minimum peak of analgesia (after 10 min). Conclusions: CT analgesia has been showed to be correlated with calcium depletion in brain, like that induced by opiate. This ion-depletSon-effect is common to some depressant drugs such as ethanol and reserpine, but not barbiturate. Therefore, CT which possesses intrinsic analgesic activity unaffected by naloxone and devoid of cross-tolerance to morphine, may funct ion as endogenous modulator of opiate action through modulation of cellular Ca2+ level in the CNS. It appears therefore that calcium plays a critical role in the mechanism of action of opiate and non opiate systems.