Effect of chronic clonidine treatment on transmitter release from sympathetic varicosities of the guinea-pig vas deferens.
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 microM) completely abolished evoked transmitter release from sympathetic varicosities bathed in an extracellular calcium concentration ([Ca(2+)](o)) of 2 mM. The inhibitory effect of clonidine was reduced by increasing [Ca(2+)](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 microM) 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.
Knight
D
D
The Narcotics Research Laboratory, School of Biomedical Sciences, Department of Physiology and Pharmacology, The University of Queensland, St. Lucia, Queensland, Australia.
Cunnane
T C
TC
Lavidis
N A
NA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D018377:Neurotransmitter Agents; D003000:Clonidine; D002118:Calcium