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

Knight, D., Cunnane, T. C. and Lavidis, N. A. (2001) Effect of chronic clonidine treatment on transmitter release from sympathetic varicosities of the guinea-pig vas deferens. British Journal of Pharmacology, 134 7: 1480-1486. doi:10.1038/sj.bjp.0704383


Author Knight, D.
Cunnane, T. C.
Lavidis, N. A.
Title Effect of chronic clonidine treatment on transmitter release from sympathetic varicosities of the guinea-pig vas deferens
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
Publication date 2001
Sub-type Article (original research)
DOI 10.1038/sj.bjp.0704383
Volume 134
Issue 7
Start page 1480
End page 1486
Total pages 7
Editor RA North
Place of publication UK
Publisher Nature Publishing Group
Collection year 2001
Language eng
Subject C1
320701 Autonomic Nervous System
730104 Nervous system and disorders
Abstract 1 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. 2 In chronically saline treated (CST) preparations, clonidine (0.5 muM) 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. 3 The nerve terminal impulse (NTI) was not affected by concentrations of clonidine that completely abolished evoked transmitter release. 4 Sympathetic varicosities developed a tolerance to clonidine (0.5 muM) following 7-9 days of chronic exposure to clonidine. 5 Acute withdrawal of preparations following chronic clonidine treatment (CCT) resulted in a significant (P<0.005) enhancement of neurotransmitter release (3.75 times) above control levels observed in CST preparations. 6 The present findings demonstrate an enhancement of neurotransmitter release from sympathetic varicosities following acute withdrawal from chronic clonidine treatment.
Keyword Pharmacology & Pharmacy
Acute Withdrawal
Clonidine
Guinea-pig
Neurotransmission
Sympathetic Varicosities
Tolerance
External Calcium-concentration
Junction Potential Amplitude
Locus Coeruleus Neurons
Nerve-terminals
Probabilistic Secretion
Alpha-adrenoceptors
Receptor Agonists
Cross-tolerance
Brain-slices
Inhibition
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 14 Aug 2007, 16:46:59 EST