BackgroundBotulinum neurotoxin type A (BoNT/A) is emerging as a treatment modality for Raynaud’s phenomenon (RP). However, the mechanism of the role of BoNT/A in antagonizing the constriction of arteriola in RP remains unclear.Materials and methodsWe tested the constriction of arteriole diameter and the distribution of adrenergic receptors on the rat cremaster modle. Moreover, we measured the secretion of norepinephrine (NE), protein level changes and related receptors on cultured rat superior cervical ganglia neurons(SCGNs), a model of sympathetic neuron.ResultsBased on our results, the inhibition of arteriole vasoconstriction was increased with increasing doses of BoNT/A. BoNT/A, prazosin, and BQ123 treatment can result in significant inhibition of arteriole vasoconstriction with the same electrical stimulation. The inhibition effect of prazosin was equivalent to BoNT/A, while BQ123 has a synergistic effect with BoNT/A. After treating SCGNs using BoNT/A for 30 min, the decrease in fluorescence intensity of FM1-43 slowed down which was correlated with the doses of BoNT/A. Furthermore, release of NE in the supernatant was significantly decreased as measured by enzyme-linked immunosorbent assay, 24 h after a high dose of BoNT/A (25 µ/mL). Cleaved-SNAP-25 was detected by Western blotting 24 h following BoNT/A (50 µ/mL) treatment. Moreover, receptor SV2C, GM1, and FGFR3 were detected on sympathetic neurons, similarly to cholinergic neurons.ConclusionOur study showed that BoNT/A could significantly inhibit electrical stimulation-induced arteriole vasoconstriction through the sympathetic pathway. The mechanism was similar to the cholinergic one, in which the vesicle release of sympathetic neurons could be inhibited by cleavage of SNAP-25. The end result was blocked vesicle fusion with the presynaptic membrane after BoNT/A treatment, inhibiting the release of the NE.
The association between cutaneous adverse drug reactions (cADRs) caused by antiepileptic drugs (AEDs) and human leukocyte antigen-A (HLA-A) and HLA-B genes in Chinese Han population in Shanghai was investigated. Through the case-control study, 30 child patients with AED-induced cADRs (cADRs group), 60 AED-tolerant child patients (AED-tolerant group) and 60 normal children not taking AEDs (normal group) were collected. The HLA-B*15:02 and HLA-A*31:01 genotypes were detected using the polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) probe method, and the correlation of HLA-B*15:02 and HLA-A*31:01 genes with the incidence of cADRs was analyzed. The positive rate of HLA-B*15:02 gene was 83.33% in the cADRs group, which was significantly increased compared with that in the AED-tolerant and normal groups (P<0.01). The positive rate of HLA-A*31:01 gene was 63.33% in the cADRs group, which was obviously increased compared with that in the AED-tolerant and normal groups (P<0.01). There were no significant differences in HLA-B*15:02 and HLA-A*31:01 genotypes between the AED-tolerant and normal groups (P>0.05). The results showed that HLA-B*15:02 and HLA-A*31:01 are significantly associated with cADRs in a Chinese Han population in Shanghai, suggesting that HLA-B*15:02 and HLA-A*31:01 genotypes should be detected in the application of AEDs.
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