Alpha 2-adrenoceptor mediated inhibition of exocytotic noradrenaline release in the absence of extracellular Ca2+.
The effect of the alpha 2-adrenoceptor agonist clonidine on 3,4-diaminopyridine (3,4-DAP)-evoked [3H]noradrenaline ([32H]NA) release in rat hippocampus slices was studied in the presence or absence (+1 mM EGTA) of extracellular Ca2+. 3H overflow (consisting mainly of unmetabolized [3H]NA) was evoked by addition of 100 microM 3,4-DAP for 10 min to the medium, which always contained 1 microM desipramine. Ligands for L-type voltage-sensitive Ca2+ channels (VSCC) did not affect the evoked [3H]NA release, whereas the preferential N-type VSCC antagonist omega-conotoxin was inhibitory, both in the presence and even more potently in the absence of Ca2+, suggesting an involvement of N-type VSCC in the mechanism of 3,4-DAP-evoked [3H]NA release. In the absence of extracellular Ca2+ the initial Na+ influx, which has been previously proposed to liberate Ca2+ from intracellular stores for the exocytotic process, most probably occurs via N-type VSCC. Clonidine inhibited the 3,4-DAP-evoked [3H]NA release in a concentration-dependent manner, both in the presence and even more potently in the absence of Ca2+; its effects were antagonized by yohimbine. In the presence of extracellular Ca2+ the clonidine effect was not changed by addition of omega-conotoxin. Similar effects of clonidine were found in slices from the rabbit hippocampus. Since the availability of Ca2+ from intracellular stores seems to predominate in the present model, our results lend some support to the suggestion that alpha 2-adrenoceptor activation might affect intracellular mechanisms of Ca2+ homeostasis.(ABSTRACT TRUNCATED AT 250 WORDS)
Jackisch
R
R
Institut für Pharmakologie und Toxikologie, Universität Freiburg, Germany.
Huang
H Y
HY
Rensing
H
H
Lauth
D
D
Allgaier
C
C
Hertting
G
G
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001369:Axons / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D005110:Extracellular Space / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D009411:Nerve Endings / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D008024:Ligands; D010456:Peptides, Cyclic; D011942:Receptors, Adrenergic, alpha; D020960:omega-Conotoxins; C053423:Conus magus toxin; D015761:4-Aminopyridine; D003000:Clonidine; D000077770:Amifampridine; D002118:Calcium; D009638:Norepinephrine