Opposing effects by pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide on hippocampal synaptic transmission.
Pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), and their receptors have been localized within the hippocampus but their physiological function on synaptic transmission is still unclear. We investigated the effects of PACAP and VIP on evoked excitatory postsynaptic currents (EPSCs) recorded with patch clamp from CA1 pyramidal neurons in rat hippocampal slices. Bath application of PACAP reversibly reduced EPSC amplitude. This effect was partly prevented by intracellular addition of (R)-adenosine, cyclic 3',5'-hydrogenphosphorothioate (cAMPS-Rp), a cAMP antagonist inhibiting protein kinase A, but not by the calcium chelator 1,2-bis (2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Application of VIP induced a long-lasting increase of EPSC amplitude that was completely abolished when cAMPS-Rp was included in the intracellular solution. PACAP and VIP effects on EPSCs were mimicked by the cAMP agonist 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP). The differing abilities of PACAP and VIP to modulate transmission efficiency over long periods of time, through the cAMP/PKA pathway, suggest that these neuropeptides may exert opposing roles in synaptic plasticity.
Ciranna
Lucia
L
Department of Physiological Sciences, University of Catania, 95125 Catania, Italy. ciranna@unict.it
Cavallaro
Sebastiano
S
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000819:agonists / Q000037:antagonists & inhibitors; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; D002614:Chelating Agents; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D004533:Egtazic Acid; D000242:Cyclic AMP; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid