Studies on the interaction between presynaptic alpha 2-adrenoceptors and adenosine A1 receptors located on noradrenergic nerve terminals.
The aim of the present study was to obtain a more detailed understanding of the interaction between presynaptic alpha 2-adrenoceptors and A1 adenosine receptors mediating inhibition of noradrenaline release in the central nervous system. Slices of rabbit hippocampus, prelabelled with [3H]noradrenaline, were superfused in the presence of the re-uptake inhibitor (+)-oxaprotiline and electrically stimulated during superfusion. During stimulation with 36 pulses at 3 Hz the alpha 2-adrenoceptor antagonist yohimbine induced a five-fold increase of noradrenaline release indicating a pronounced autoinhibition of approximately 80%. In these experiments the inhibition of release caused by R-PIA, a preferential A1 agonist, as well as its facilitation caused by DPCPX, a selective A1 antagonist, were smaller in comparison to the effects of these compounds on release virtually free of autoinhibition (i.e. by stimulating the tissue with 4 pulses at 100 Hz (POP-stimulation) or with 36 pulses at 3 Hz in presence of yohimbine). Clonidine, an alpha 2-adrenoceptor agonist, was used to impose a distinct alpha 2-adrenoceptor-mediated inhibition of release elicited by POP-stimulation. Only, however, in the presence of 30 nmol/l clonidine, causing maximum inhibition of approximately 80% of 3H-overflow, but not in the presence of 6 nmol/l clonidine, causing approximately 50% inhibition, a significant diminution of the inhibitory effect of R-PIA was seen. Similarly, the alpha 2-adrenoceptor mechanism was affected only by 10 mumols/l R-PIA causing maximum inhibition of approximately 80%, but remained unchanged in the presence of 30 nmol/l R-PIA diminishing release by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
Allgaier
C
C
Institute of Pharmacology and Toxicology, University of Freiburg, Federal Republic of Germany.
Greber
R
R
Hertting
G
G
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011983:Receptors, Purinergic; D014970:Xanthines; D010660:Phenylisopropyladenosine; D015016:Yohimbine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D003000:Clonidine; D009638:Norepinephrine