Abstract
BACKGROUND: Cyclohexylamine (CHA) is a principal metabolite of cyclamate, which was once one of the most prominently consumed non-sugar sweeteners. Earlier studies suggested that long-term use of cyclamate might be carcinogenic and genotoxic; however, no consistent evidence supports an association between cyclamate and cancer risk. However, this issue remains interesting. Cyclamate can be metabolized to CHA by the intestinal bacteria in humans and some animals. Previous reports indicated CHA could induce atrophy of rat testes and affect rat fertility, as well as contract rat vas deferens. However, the contractile mechanisms of CHA on rat vas deferens remains poorly understood. This study investigated the contractile mechanisms of CHA on the isolated rat epididymal portion of the vas deferens. METHODS: Male S.D. rats weighing between 200 g and 250 g were used. The isolated epididymal portion of rat vas deferens was added to calcium-channel blockers, calcium-free conditions or various concentrations (1 × 10(-8) M-1 × 10(-5) M) of adrenergic antagonists and CHA (1 × 10(-4) M). RESULTS: CHA (1 × 10(-5) M-1 × 10(-1) M) evoked a concentration-dependent contraction. Calcium-channel blocker, nifedipine (1 × 10(-8)M-1 × 10(-6) M) or verapamil (1 × 10(-8)M-1 × 10(-5) M) pretreatment, dose-dependently attenuated the CHA (1 × 10(-4) M)-induced contraction. The calcium-free condition completely blocked CHA (1 × 10(-4) M)-induced contraction. Prazosin (1 × 10(-8)M-1 × 10(-6) M) or yohimbine (1 × 10(-7) M-1 × 10(-5) M) pretreatment or treatment could inhibit contractions evoked by CHA (1 × 10(-4) M) in a dose-dependent manner. Moreover, the effect of CHA (1 × 10(-4) M) was entirely blocked by combining prazosin and yohimbine pretreatment. WB4101 (1 × 10(-8) M) could completely inhibit the contractions induced by CHA (1 × 10(-4) M). CEC (1 × 10(-8) M-1 × 10(-4) M) showed no significant inhibitory effect on the contractile tension but reduced the frequency induced by CHA (1 × 10(-4) M). Moreover, reserpine (1 × 10(-5) M) showed a significant inhibition on the contractions of CHA (1 × 10(-4) M). CONCLUSIONS: From the above results, CHA-contracts epididymal vas deferens of rats by affecting endogenous catecholamine release via postsynaptic α(1A)- and presynaptic α(2)- adrenoceptors and are calcium-dependent.