Characterization of imidazole binding sites labeled by /sup 3/H-p-aminoclonidine in the bovine ventrolateral medulla (VLM)
Since vasodepressor responses to clonidine (CLON) are mediated by neurons in the C1 area of VLM, and CLON, an imidazole (IM), bind to IM as well as alpha-adrenergic receptors in brain, the authors characterized binding sites for CLON in RVL. IM sites were measured in preincubated, washed P/sub 2/ membranes (0.1 mg protein/ml) of YLM using /sup 3/H-p-aminoclonidine (/sup 3/H-PAC) as a radioligand (40 min., 25/sup 0/C). (-)-Norepinephrine (NE; 10 ..mu..M) inhibited only 70% of specific /sup 3/H-PAC binding (1.0 nM) as defined by 10 ..mu..M phentolamine. The sites displaced by NE resemble alpha/sub 2/-adrenergic receptors. When 10..mu..M NE was included in the incubation medium, the remaining /sup 3/H-PAC sites had a high affinity for CLON (IC/sub 50/ = 6 +/- 1 nM) and were saturable (K/sub D/ = 1.5 +/- 0.4 nM). Imidazole-4-acetic acid (IC/sub 50/ = 800 +/- 23 nM) and cimetadine (IC/sub 50/ = 480 +/- 88 nM) potently inhibited these non-adrenergic sites, but did not affect total /sup 3/H-PAC binding to cerebral cortical membranes indicating regional specificity. Histamine was a weak inhibitor (IC/sub 50/ = 38 +/- 3 ..mu..M) in cortex, but was more potent (IC/sub 50/ = 2 +/- 1 ..mu..M) in the RVL. The putative endogenous ligand clonidine displacing substance (CDS), has a 9-fold selectivity of the IM component of /sup 3/H-PAC binding in VLM. The authors conclude CLON binds to IM and adrenergic recognition sites in VLM. Binding to one or both sites may mediate the vasodepressor VLM. Binding to one or both sites may mediate the vasodepressor actions of the drug actions of the drug.
- Research Organization:
- Cornell Univ. Medical College, New York, NY
- OSTI ID:
- 5393581
- Report Number(s):
- CONF-8604222-; TRN: 86-028331
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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550201* - Biochemistry- Tracer Techniques