Presynaptic alpha 2-adrenoceptor modulation of 5-hydroxytryptamine and noradrenaline release from vascular adrenergic nerves.
Modulation of the stimulation-evoked release of 5-hydroxytryptamine (5-HT) and noradrenaline (NA) by presynaptic alpha 2-adrenoceptors was characterized in the perfused mesenteric vascular bed of the rat. The vasoconstrictor response to periarterial nerve stimulation (PNS; 8 Hz), previously abolished in the presence of 30 nM prazosin, was restored after 15 min treatment with 10 microM 5-HT, without a significant effect on the pressor response to 1 nmol of infused NA, which was previously abolished with prazosin. The restored pressor response to PNS was abolished by 100 nM tetrodotoxin and 100 nM ketanserin. Clonidine (1-10 microM) in the presence of prazosin induced a dose-dependent potentiation of the restored pressor response to PNS after 5-HT treatment while BHT 920 (10 nM-1 microM) and 100 nM clonidine inhibited the restored response. In the presence of 100 nM phentolamine, the restored pressor response to PNS was not altered by clonidine, but was inhibited by BHT 920. The PNS (8 Hz)-evoked tritium release in a preparation labeled with [3H]5-HT was facilitated by clonidine (100 nM-10 microM) while BHT 920 (10 nM-1 microM) and cocaine (1-10 microM) reduced the release. Yohimbine (1 microM) antagonized the effects of clonidine and cocaine but not of BHT 920 on the PNS-evoked tritium release. In the preparation labeled with [3H]NA, clonidine did not alter the PNS-evoked tritium release while BHT 920 inhibited it and cocaine facilitated it. Yohimbine did not antagonize the effect of BHT 920.(ABSTRACT TRUNCATED AT 250 WORDS)
Kawasaki
H
H
Department of Pharmacology, Miyazaki Medical College, Japan.
Urabe
M
M
Takasaki
K
K
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013152:Splanchnic Circulation / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; C024763:talipexole; D003042:Cocaine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine