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Articles in PresS, published online ahead of print August 29, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00477.2002
Submitted on June 6, 2002
Accepted on August 22, 2002
1 Centre for Neuroscience, Flinders University, Adelaide, SA, Australia; Anatomy & Histology, Flinders University, Adelaide, SA, Australia
* To whom correspondence should be addressed. E-mail: Judy.Morris{at}flinders.edu.au.
We examined effects of botulinum neurotoxin A (BoNTA) on sympathetic constrictions of the vena cava and uterine artery from guinea-pigs, to test the role of soluble NSF attachment protein receptor (SNARE) proteins in release of the cotransmitters norepinephrine (NE) and neuropeptide Y (NPY). Protein extracts of venae cavae and uterine arteries showed partial cleavage of synaptosomal associated protein of 25 kDa (SNAP-25) after treatment in vitro with BoNTA (50-100nM). The rising phase of isometric contractions of isolated venae cavae to field stimulation at 20Hz, mediated by NE acting on 
-adrenoceptors, was reduced significantly by 100nM BoNTA. However, sustained sympathetic contractions mediated by NPY were not affected by BoNTA. In uterine arteries, noradrenergic contractions to 1Hz stimulation were almost abolished by BoNTA, and contractions at 10Hz were reduced by 50-60%. We conclude that SNARE proteins are involved in exocytosis of NE from synaptic vesicles at low frequencies of stimulation, but may not be essential for exocytosis of NPY and NE from large vesicles at high stimulation frequencies.
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