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The Journal of Neuroscience, January 1, 1999, 19(1):180-192

Regulation and Immunohistochemical Localization of -Stimulated Adenylyl Cyclases in Mouse Hippocampus

Lauren P. Baker, Mark D. Nielsen, Soren Impey, Beth M. Hacker, Steven W. Poser, Mandy Y. M. Chan, and Daniel R. Storm

Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280

Specific forms of synaptic plasticity such as long-term potentiation (LTP) are modulated by or require increases in cAMP. The various adenylyl cyclase isoforms possess unique regulatory properties, and thus cAMP increases in a given cell type or tissue in response to converging signals are subject to the properties of the adenylyl cyclase isoforms expressed. In most tissues, adenylyl cyclase activity is stimulated by neurotransmitters or hormones via stimulatory G-protein (G_s)-coupled receptors and is inhibited via inhibitory G-protein (G_i)-linked receptors. However, in the hippocampus, stimulation of G_i-coupled receptors potentiates G_s-stimulated cAMP levels. This effect may be associated with the regulatory properties of adenylyl cyclase types 2 and 4 (AC2 and AC4), isoforms that are potentiated by the subunit of G_i in vitro. Although AC2 has been shown to be stimulated by in whole cells, reports describing the sensitivity of AC4 to in vivo have yet to emerge. Our results demonstrate that G_s-mediated stimulation of AC4 is potentiated by released from activated G_i-coupled receptors in intact human embryonic kidney (HEK) 293 cells. Furthermore, we show that the AC2 and AC4 proteins are expressed in the mouse hippocampal formation and that they colocalize with MAP2, a dendritic and/or postsynaptic marker. The presence of AC2 and AC4 in the hippocampus and the ability of each of these enzymes to detect coincident activation of G_s- and G_i-coupled receptors suggest that they may play a crucial role in certain forms of synaptic plasticity by coordinating such overlapping synaptic inputs.

Key words: adenylyl cyclase; cAMP; G-protein; ; hippocampus; synaptic plasticity; immunohistochemistry; immunocytochemistry

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Copyright © 1999 Society for Neuroscience  0270-6474/99/191180-13$05.00/0

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