Effects of taurine and some structurally related analogues on the central mechanism of thermoregulation: a structure-activity relationship study.
There is large body of evidences on the role of taurine in the central mechanisms of thermoregulation in mammals, but it is not clear, whether the hypothermic effect of taurine depends on its interaction with GABA receptors or with a specific receptor. In order to answer this question, we have performed a structure-activity relationship study by using both in vitro and in vivo preparations. MicroM amounts of taurine or each of 20 analogues were injected intracerebroventricularly in conscious, restrained rabbits while rectal temperature was recorded. Receptor-binding studies, with synaptic membrane preparations from rabbit brain were used to determine the affinities of these compounds for GABA(A) and GABA(B) receptors. Furthermore, the interaction with presynaptic GABA and taurine uptake systems was studied using crude synaptosomal preparations from rabbit brain. Among the compounds tested, (+/-)-cis-2-aminocyclohexanesulfonic acid, induced hypothermia, but did not interact with GABA(A) and GABA(B) receptors neither did it affect GABA and taurine uptake, thus suggesting that its effect on body temperature is not mediated by the central GABAergic system. Interestingly, the trans-isomer was devoid of effects either in vivo or in vitro. In order to explain (+/-)-cis-2-aminocyclohexanesulfonic acid-induced hypothermia, a stereoscopic model was produced showing its possible interactions with a putative taurine brain receptor.
Frosini
M
M
Istituto di Scienze Farmacologiche, Università di Siena, Italy.
Sesti
C
C
Saponara
S
S
Donati
A
A
Palmi
M
M
Valoti
M
M
Machetti
F
F
Sgaragli
G
G
D000818:Animals; D001831:Body Temperature; D001833:Body Temperature Regulation / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008297:Male; D011817:Rabbits; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013654:Taurine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D013654:Taurine; D005680:gamma-Aminobutyric Acid