Age-related changes in the antinociception induced by taurine in mice.

Taurine is a nonessential amino acid that is of medical interest for the nutrition of infants. Taurine has been found in the central nervous system of rodents and humans, and among its potential therapeutic uses, it is interesting to remark its analgesic actions. It is also well known that concentration levels during the fetal and prenatal periods are higher than in adulthood. The data obtained so far indicate that taurine is involved in the development process of the brain and possibly other organs. The taurine levels in old age are still unknown, but it is presumed that they will be different from those of younger animals. Data about age-related alterations and functional modifications of this and other amino acids are still scarce. The aim of the present work was to study the antinociceptive effect of taurine and its relationship with aging in mice. No differences were found between prepubertal and young adult animals; on the contrary, old animals showed significantly reduced sensitivity to the antinociception induced by taurine; in fact, at the tested doses, taurine did not induce antinociception in this group of mice. The mechanism underlying this effect has not been clarified because there are several mechanisms and neurotransmitter systems involved in the antinociception induced by taurine.

Role of K+ -channels in homotaurine-induced analgesia.

In previous articles, antinociceptive activity for homotaurine has been demonstrated to be mediated by opioid, GABAergic and cholinergic mechanisms. GABAB-agonists affect K+-channels and it is known that K+-channels modulate specific activation of opioid receptors. In this study, we examined the involvement of K+-channels in the antinociceptive activity of homotaurine (22-445 mg/kg). Antinociceptive response was obtained after icv pretreatment with the channel specific blockers 4-aminopyridine (voltage-dependent channels), tetraethylammonium (Ca++ and voltage-dependent) and gliquidone (ATP-dependent). The nociceptive tests performed were acetic acid induced abdominal constriction (mice) and tail flick (rats) tests. Acetic acid responses to homotaurine were inhibited by tetraethylammonium (5 microg) and gliquidone (16 microg). Tail flick response to homotaurine was inhibited by tetraethylammonium (50 microg), gliquidone (40 and 80 microg) and 4-aminopyridine (25 and 250 ng). These results suggest an involvement of the three types of K+-channels in antinociception by homotaurine, depending on specific homotaurine and blocker doses. At a spinal level, they appear to be involved together with GABAB and opioid mechanisms. Peripherally, only tetraethylammonium channels would be substantially activated during homotaurine antinociceptive effect.

GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia.

1. The involvement of GABA(B) receptors and opioid mechanisms in homotaurine-induced analgesia has been investigated in current models of nociception by using a GABA(B) receptor antagonist, morphine, and naloxone. CGP 35348 (50-200 mg/kg IP), a highly selective GABA(B) antagonist, was administered prior to carrying out a dose-response curve of homotaurine (22.6-445 mg/kg IP) antinociceptive effect in the abdominal constriction (mice) and tail flick (rats) tests. 2. The tail flick test was performed in animals pretreated with morphine (0.5 mg/kg SC) and naloxone (1 mg/kg), 15 min before amino acid. Animals treated with saline 10 ml/kg (mice) or 1.25 ml/kg (rats) were included as control for the vehicle used. 3. CGP 35348 antagonized the antinociceptive effect of homotaurine in both tests. The range of doses affected by the interaction depended on the test assayed, but it was coincident for the main part of the dose-response curve. 4. A subanalgesic dose of morphine potentiated the antinociceptive effect of lower doses of homotaurine in the tail flick test. Naloxone pretreatment inhibited the antinociceptive effect of homotaurine. 5. These data imply that GABA(B) receptor subpopulations and opiate mechanisms are involved in the antinociceptive effect of homotaurine. Because functional relationships have been found between GABAergic and opiate systems in analgesic effects, an interaction of the two mechanisms may be operating in the effects described for homotaurine.