Effect of chronic clonidine treatment on transmitter release from sympathetic varicosities of the guinea‐pig vas deferens

Previous studies have demonstrated that chronic pre‐synaptic inhibition of transmitter release by morphine evokes a counter‐adaptive response in the sympathetic nerve terminals that manifests itself as an increase in transmitter release during acute withdrawal. In the present study we examined the p...

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Bibliographic Details
Published in:British journal of pharmacology 2001-12, Vol.134 (7), p.1480-1486
Main Authors: Knight, David, Cunnane, Tom C, Lavidis, Nickolas A
Format: Article
Language:English
Subjects:
Acute withdrawal
Adrenergic alpha-Agonists - pharmacology
Animals
Biological and medical sciences
Calcium - pharmacology
Catecholaminergic system
clonidine
Clonidine - pharmacology
Dose-Response Relationship, Drug
Guinea Pigs
guinea‐pig
In Vitro Techniques
Male
Medical sciences
Neuromuscular Junction - drug effects
Neuromuscular Junction - physiology
Neuropharmacology
neurotransmission
Neurotransmitter Agents - secretion
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Sympathetic Fibers, Postganglionic - drug effects
Sympathetic Fibers, Postganglionic - metabolism
sympathetic varicosities
tolerance
Vas Deferens - drug effects
Vas Deferens - innervation
Vas Deferens - metabolism
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Summary:Previous studies have demonstrated that chronic pre‐synaptic inhibition of transmitter release by morphine evokes a counter‐adaptive response in the sympathetic nerve terminals that manifests itself as an increase in transmitter release during acute withdrawal. In the present study we examined the possibility that other pre‐synaptically acting drugs such as clonidine also evoke a counter‐adaptive response in the sympathetic nerve terminals. In chronically saline treated (CST) preparations, clonidine (0.5 μM) completely abolished evoked transmitter release from sympathetic varicosities bathed in an extracellular calcium concentration ([Ca2+]o) of 2 mM. The inhibitory effect of clonidine was reduced by increasing [Ca2+]o from 2 to 4 mM and the stimulation frequency from 0.1 to 1 Hz. The nerve terminal impulse (NTI) was not affected by concentrations of clonidine that completely abolished evoked transmitter release. Sympathetic varicosities developed a tolerance to clonidine (0.5 μM) following 7 – 9 days of chronic exposure to clonidine. Acute withdrawal of preparations following chronic clonidine treatment (CCT) resulted in a significant (P
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0704383