Dual effects of clonidine on rat prejunctional alpha-adrenoceptors.
1. The effects of clonidine (1.0 mumol/l) and phentolamine (3.0 mumol/l) on the stimulation-induced efflux of radioactivity were assessed in rat isolated atria and tail arteries in which transmitter stores had been labelled with (3H)-noradrenaline. 2. In atria, clonidine did not affect transmitter release when stimulation was for 10 s periods at frequencies of 1, 2 or 5 Hz, whereas at 10 Hz there was a significant 1.2-fold enhancement of release. Phentolamine enhanced release with stimulation at 5 Hz and 10 Hz by 1.5- and 2.5-fold respectively. 3. In tail arteries, clonidine reduced release when stimulation was for 30 s periods at a frequency of 1 Hz, but did not affect release at 2 Hz or 5 Hz. Phentolamine in each case produced an approximately 1.5-fold enhancement of release. 4. In the pithed rat, spinal stimulation of cardioaccelerator fibres produced a tachycardia, the magnitude of which depended on the frequency and duration of stimulation. Clonidine (10 micrograms/kg, i.v.) caused either a reduction or an enhancement of the response depending on the frequency and duration of stimulation; in the presence of phentolamine (2 mg/kg, i.v.), clonidine had no effect. 5. The results are consistent with partial agonistic actions of clonidine at prejunctional alpha-adrenoceptors in the rat cardiovascular system; such effects may be of relevance to the mechanism of the clonidine withdrawal syndrome.
D000818:Animals; D001158:Arteries / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects; D006325:Heart Atria; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013610:Tachycardia / Q000188:drug therapy; D013623:Tail / Q000098:blood supply
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine