Presynaptic cross-talk of beta-adrenoreceptor and 5-hydroxytryptamine receptor signalling in the modulation of glutamate release from cerebrocortical nerve terminals.
1. The presynaptic interactions between facilitatory beta-adrenoreceptors and inhibitory 5-hydroxytryptamine (5-HT) receptors modulating glutamate release from cerebrocortical nerve terminals were examined. 2. 4-aminopyridine (4-AP, 1 mM)-evoked glutamate release was facilitated by the membrane permeant cyclic-3',5'-adenosine monophosphate (cAMP) analogue, 8-bromo-cAMP (8-Br-cAMP), used to directly activate cAMP-dependent protein kinase (PKA). 3. The beta-adrenoreceptor agonist, isoprenaline (ISO), effected a concentration-dependent potentiation of 4-AP-evoked glutamate release which was abolished by the beta-adrenoreceptor antagonist, propranolol, and the PKA inhibitor, Rp-cyclic-3',5'-adenosine-monophosphothioate (Rp-cAMPS). 4. 5-HT receptor activation by 100 microM 5-HT produced an inhibition of 4-AP-evoked glutamate release in nerve terminals. The inhibitory effect of 5-HT could be mimicked by the selective 5-HT(1A) receptor agonist, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and antagonized by 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190). 5. When 5-HT (or 8-OH-DPAT) was used in conjunction with ISO or 8-Br-cAMP, the beta-adrenoreceptor- and PKA-mediated potentiation of glutamate release was abrogated. 6. The inhibitory crosstalk of 5-HT(1A) receptors to beta-adrenoceptor-mediated facilitation of glutamate release was abolished in the presence of NAN-190. 7. Examination of voltage-dependent Ca(2+) influx revealed that, while ISO and 5-HT alone caused a respective potentiation and diminution of the 4-AP-evoked increase in [Ca(2+)](c), the co-presence of 5-HT abolished the ISO mediated potentiation of Ca(2+) influx. 8. Together, these results suggest that beta-adrenoreceptors and 5-HT(1A) receptors coexist on the cerebrocortical nerve terminals and that the cross-talk between the two receptor signalling pathways occurs at a locus downstream from cAMP production, possibly at the level of voltage-dependent Ca(2+) influx.
Wang
Su-Jane
SJ
Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT, U.K.
Coutinho
Victoria
V
Sihra
Talvinder S
TS
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D018698:Glutamic Acid