@article {Hillman1062, author = {Kristin L. Hillman and Van A. Doze and James E. Porter}, title = {α1A-Adrenergic Receptors Are Functionally Expressed by a Subpopulation of Cornu Ammonis 1 Interneurons in Rat Hippocampus}, volume = {321}, number = {3}, pages = {1062--1068}, year = {2007}, doi = {10.1124/jpet.106.119297}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {The importance of adrenergic receptors (ARs) in the hippocampus has generally focused on βARs; however, interest is growing in hippocampal αARs given their purported neuroprotective role. We have previously reported α1AR transcripts in a subpopulation of cornu ammonis 1 (CA1) interneurons. The goal of this study was to identify the specific α1AR subtype (α1A, α1B, α1D) functionally expressed by these cells. Using cell-attached recordings to measure action potential frequency changes, concentration-response curves for the selective α1AR agonist phenylephrine (PE) were generated in the presence of competitive subtype-selective α1AR antagonists. Schild regression analysis was then used to estimate equilibrium dissociation constants (Kb) for each receptor antagonist in our system. The selective α1AAR antagonists, 5-methylurapidil and WB-4101 [2-[(2,6-dimethoxyphenoxyethyl)aminomethyl]-1,4-benzodioxane hydrochloride], produced consecutive rightward shifts in the concentration-response curve for PE when used at discriminating, nanomolar concentrations. Calculated Kb values for 5-methylurapidil (10 nM) and WB-4101 (5 nM) correlate to previously published affinity values for these antagonists at the α1AAR. The selective α1BAR antagonist L-765,314 [(2S)-4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-2-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperazinecarboxylic acid], as well as the selective α1DAR antagonist BMY7378 [8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride], produced significant rightward shifts in the concentration-response curve for PE only when used at nondistinguishing, micromolar concentrations. Calculated Kb values for L-765,314 (794 nM) and BMY7378 (316 nM) do not agree with affinity values for these antagonists at the α1B or α1DAR, respectively. Rather, these Kb values more closely match equilibrium dissociation constants estimated for these compounds when used to identify α1AAR subtypes. Together, our results provide strong evidence to support functional expression of α1AARs in a subpopulation of CA1 interneurons. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/321/3/1062}, eprint = {https://jpet.aspetjournals.org/content/321/3/1062.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }