ABSTRACT
Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.
Subject(s)
Animals , Male , Jejunum/drug effects , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Myosins/metabolism , Taurine/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Atropine/pharmacology , Calcium Channel Blockers/pharmacology , Cimetidine/pharmacology , Diphenhydramine/pharmacology , Enteric Nervous System/drug effects , Histamine H1 Antagonists/pharmacology , /pharmacology , Jejunum/physiology , Muscarinic Antagonists/pharmacology , Myosin-Light-Chain Kinase/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide/metabolism , Phosphorylation , Phentolamine/pharmacology , Propranolol/pharmacology , Rats, Sprague-Dawley , Taurine/antagonists & inhibitors , Tetrodotoxin/pharmacology , Verapamil/pharmacologyABSTRACT
The effect of taurine on nociception was investigated in adult male Swiss mice using the formalin and acetic acid tests. Taurine (50-200 mg/kg) injected sc into the animals (N = 6 per group) 30 min before formalin injection into the right hind paw reduced formalin-induced early phase (0-5 min) licking activity by 30-42 per cent , but had no effect on the late phase (20-25 min) response. Writhing responses induced by acetic acid injected ip were also significantly inhibited by 49 per cent and 56 per cent by doses of 100 and 200 mg/kg taurine, respectively. In both tests taurine demonstrated antinociception which was significantly blocked by naloxone (1 mg/kg, sc, administered simultaneously with taurine). The naloxone-sensitive antinociceptive action of taurine was probably mediated via modulation of endogenous pain-regulatory systems that involve opioid peptides, neuropeptides like substance P and amino acids such as glutamate and aspartate