The involvement of PACAP/VIP system in the synaptic transmission in the hippocampus.
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two closely related peptides, which can activate protein kinase A (PKA). At least three receptors for PACAP and VIP have been identified. The PACAP-specific receptor, PAC1 receptor, exhibits a higher affinity for PACAP than VIP, whereas VIP receptors, VPAC1-R and VPAC2-R, have similar affinities for PACAP and VIP. Both PACAP/VIP and their cognate receptors are highly expressed in the brain, including the hippocampus. Recently, their roles in the regulation of synaptic transmission have begun to emerge. PACAP/VIP can signal through different pathways to regulate N-methyl-D: -aspartate (NMDA) receptors in CA1 pyramidal cells. The activation of VPAC1/2-Rs increases evoked NMDA currents via the cyclic AMP/PKA pathway. However, the activation of PAC1-R stimulates a PLC/PKC/Pyk2/Src signaling pathway to enhance NMDA receptor function in hippocampal neurons. Furthermore, different concentrations of PACAP induce different effects on the both α-amino-3-hydroxy-5-isoxazole-propionic acid-evoked current and basal synaptic transmission by activating different receptors. Their roles in learning and memory are also demonstrated using transgenic mice and pharmacological methods.
Yang
Kai
K
Department of Physiology, University of Toronto, I King's College Circle, Toronto, ON, Canada.
Lei
Gang
G
Jackson
Michael F
MF
Macdonald
John F
JF
D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016194:Receptors, N-Methyl-D-Aspartate; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid