Cyclic AMP-generating systems in rat hippocampal slices.
Properties of the norepinephrine (NE) stimulated, cAMP-generating system were studied in rat hippocampal slices. NE but not other putative neurotransmitters, caused a 3--4-fold rise in cAMP levels in the slices. All 3 main subdivisions of the hippocampus (HPC), the dentate gyrus, areas CA3 and CA1, possessed the capacity to produce cAMP. The latency to the NE stimulation of cAMP formation was about 20 sec but maximal stimulation was reached only after 5--10 min of incubation. Intrahippocampal injection of kainic acid (KA) caused a nearly complete destruction of hippocampal neurons and a marked increase in number of glial cells. NE caused a 12--15-fold rise in cAMP levels in KA-treated HPC. Compared to normal HPC where potency order of noradrenergic agonists indicated activation of a beta-1 receptor type, the pattern for the KA-treated HPC indicated the dominance of beta-2 receptors. The beta-1 antagonist, practolol, and the beta-2 antagonist, H35/25, were about equipotent in blocking the NE-stimulated cAMP formation in normal HPC. In KA-treated HPC, on the other hand, H35/25 was much more potent than practolol in inhibiting NE-stimulated cAMP formation. It is suggested that in the HPC beta-1 adrenergic receptors are primarily neuronal and beta-2 receptors, glial, and that activation of both receptor species results in activation of a cAMP-generating system.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D018377:Neurotransmitter Agents; D011943:Receptors, Adrenergic, beta; D006632:Histamine; D000242:Cyclic AMP; D000241:Adenosine; D007608:Kainic Acid; D009638:Norepinephrine