Action of botulinum toxin on transmission from sympathetic nerves to the vas deferens

Holman, Mollie E.; Spitzer, Nicholas C.

doi:10.1111/j.1476-5381.1973.tb08343.x

Cited by 20 publications

(5 citation statements)

References 11 publications

(14 reference statements)

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“…The partial inhibition of noradrenergic neurotransmission from sympathetic vasoconstrictor neurons produced by BoNTA, with the same regime of treatment that completely inhibited cholinergic neurotransmission, is also consistent with previous studies (14,28) of autonomic neurons. Although neuropeptide Y (NPY) acts as a vasoconstrictor cotransmitter with norepinephrine in the uterine artery, the NPY-mediated component of sympathetic vasoconstriction is slow, occurring after cessation of stimulation, and is only revealed after removal of the vasodilator neurons (34).…”

Section: Differential Effect Of Bonta On Different Classes Of Cotranssupporting

confidence: 90%

“…The regime of BoNTA treatment used in the present study was based on previous functional studies (14,16,28) of autonomic neurons showing that BoNTA incu- bated in the nanomolar range with whole tissues for several hours at 37°C produced substantial reduction or abolition of neurotransmission from some types of neurons. This treatment clearly produced cleavage of the COOH-terminal nine amino acids from SNAP-25 in the uterine artery, leaving a shortened protein of ϳ24 kDa (4).…”

Section: Cleavage Of Snap-25 By Bontamentioning

confidence: 99%

“…Experiments using botulinum or tetanus toxins to cleave specific SNARE proteins demonstrated that release of different chemical classes of neurotransmitters seems to be dependent on SNARE proteins (28,29). However, the sensitivity of transmitter release from different populations of autonomic neurons to blockade by botulinum toxins can be quite variable (14,16,20,28,35). One recent study (35) has shown that release of NO from inhibitory motor neu-rons in the guinea pig colon was not affected by botulinum toxin, whereas release of acetylcholine and substance P from excitatory motor neurons was greatly reduced, indicating differential involvement of SNARE proteins in release of these transmitters.…”

mentioning

confidence: 99%

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Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons

Morris

Jobling

Gibbins

2001

American Journal of Physiology-Heart and Circulatory Physiology

127

116

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The role of the soluble NSF attachment protein receptor (SNARE) protein complex in release of multiple cotransmitters from autonomic vasodilator neurons was examined in isolated segments of guinea pig uterine arteries treated with botulinum neurotoxin A (BoNTA; 50 nM). Western blotting of protein extracts from uterine arteries demonstrated partial cleavage of synaptosomal-associated protein of 25 kDa (SNAP-25) to a NH2-terminal fragment of approximately 24 kDa by BoNTA. BoNTA reduced the amplitude (by 70-80%) of isometric contractions of arteries in response to repeated electrical stimulation of sympathetic axons at 1 or 10 Hz. The amplitude of neurogenic relaxations mediated by neuronal nitric oxide (NO) was not affected by BoNTA, whereas the duration of peptide-mediated neurogenic relaxations to stimulation at 10 Hz was reduced (67% reduction in integrated responses). In contrast, presynaptic cholinergic inhibition of neurogenic relaxations was abolished by BoNTA. These results demonstrate that the SNARE complex has differential involvement in release of cotransmitters from the same autonomic neurons: NO release is not dependent on synaptic vesicle exocytosis, acetylcholine release from small vesicles is highly dependent on the SNARE complex, and neuropeptide release from large vesicles involves SNARE proteins that may interact differently with regulatory factors such as calcium.

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Section: Differential Effect Of Bonta On Different Classes Of Cotranssupporting

confidence: 90%

Section: Cleavage Of Snap-25 By Bontamentioning

confidence: 99%

mentioning

confidence: 99%

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Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons

Morris

Jobling

Gibbins

2001

American Journal of Physiology-Heart and Circulatory Physiology

127

116

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“…Indeed, the sympathetic tone relies on the release of norepinephrine by postganglionic sympathetic neurons occurring by exocytosis from large dense cored synaptic vesicles [26]. A sympatholytic effect of BTX-A has been repeatedly reported in different experimental settings in various animal species [27,28,29]. In a random pattern skin flap model, onabotulinumtoxinA increased vascular blood flow and viable flap area in rats by reducing norepinephrine level while NO was not affected [30].…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Intracavernosal Injections of AbobotulinumtoxinA (Dysport®) as Add on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 for Erectile Dysfunction—Case Studies

Giuliano

Joussain

Denys

2019

Toxins

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Erectile dysfunction (ED) is a highly prevalent condition with a variety of possible risk factors and/or etiologies. Despite significant advances regarding ED pharmacological management, there are still insufficient responders to existing pharmacological treatments e.g., approximately 30% of patients are insufficient responders to phosphodiesterase type 5 inhibitors (PDE5-Is). It has been recently proposed that botulinum toxin A intracavernosally (IC) delivered could be effective in these patients. Data from a retrospective uncontrolled single center study of 47 ED patients, consecutively recruited, insufficient responders to existing pharmacological treatments e.g., PDE5-Is or IC PGE1 injections treated with IC abobotulinumtoxinA 250 or 500 U as free combination with their existing treatment have been analyzed. Response rate, according to the International Index of Erectile Function-Erectile Function domain score, 6 weeks following IC abobotulinumtoxinA in combination with prior pharmacological treatment, was 54%. Two patients have reported mild penile pain on injection or during the 3 days following injection. Therapeutic efficacy did not seem to be influenced by the etiologies and/or risk factors for ED. Conversely, the less severe ED, the higher the response rate. Preliminary evidence for the therapeutical potential with acceptable safety of IC abobotulinumtoxinA as add-on therapy for ED not sufficiently responsive to standard therapy should be confirmed in randomized clinical trials.

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“…Parasympathetic activity, which controls the vasodilation of the penile arteries, can only successfully fill the penis if it follows, or at least accompanies, the initial inhibition of sympathetic activity [5]. Depression of noradrenergic transmission in the post-ganglionic nerve terminals of the sympathetic nervous system that supplies the smooth muscle was reported five decades ago [6]. Intramural BoNT/A injection throughout the whole bladder cleaves SNAP25 in adrenergic sympathetic neurons [7].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness and Safety of Intracavernosal IncobotulinumtoxinA (Xeomin®) 100 U as an Add-on Therapy to Standard Pharmacological Treatment for Difficult-to-Treat Erectile Dysfunction: A Case Series

Giuliano

Denys

Joussain

2022

Toxins

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Registered pharmacological treatments are insufficiently effective for erectile dysfunction (ED) in around 30% of affected men. Intracavernosal injection (ICI) of ona- and abobotulinumtoxinA can reduce ED in insufficient responders. We aimed to assess the safety and effectiveness of incobotulinumtoxinA ICI as an add-on therapy to phosphodiesterase-type 5 inhibitors (PDE5-Is) or prostaglandinE1 ICIs (PGE1 ICIs) to treat ED that did not respond sufficiently to this treatment alone. We retrospectively analyzed data from 66 men with difficult to treat ED treated with single or repeated incobotulinumtoxinA 100U ICI as an add-on therapy. Response rate (increase in International Index of Erectile Function-Erectile Function domain score ≥ the minimum clinically important difference) was 52% (median (1st–3rd quartile) 43.5 (34–71) days post-incobotulinumtoxinA ICI). ED etiology (except spinal cord injury) and severity did not influence effectiveness. Only a clinically significant response to the 1st injection predicted a request for a 2nd injection (OR = 5.6, 95%, CI 1.6–19.4). Three men reported mild penile pain during the injection. These results provide preliminary evidence for the effectiveness and safety of incobotulinumtoxinA ICI as an add-on therapy to treat ED that is insufficiently responsive to standard care and provides support for the multicenter randomized clinical trial NCT05196308.

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Action of botulinum toxin on transmission from sympathetic nerves to the vas deferens

Cited by 20 publications

References 11 publications

Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons

Differential inhibition by botulinum neurotoxin A of cotransmitters released from autonomic vasodilator neurons

Safety and Efficacy of Intracavernosal Injections of AbobotulinumtoxinA (Dysport®) as Add on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 for Erectile Dysfunction—Case Studies

Effectiveness and Safety of Intracavernosal IncobotulinumtoxinA (Xeomin®) 100 U as an Add-on Therapy to Standard Pharmacological Treatment for Difficult-to-Treat Erectile Dysfunction: A Case Series

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