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1 The chemoreactive ligands 5(2-(((1'-(4'-isothiocyanatophenylamino)thiocarbonyl)-amino)-2-methylpropyl)amino-2-hydroxypropoxy)-3,4-dihydrocarbostyril (DCITC) and 8-hydroxy-5(2-(((1'-(4'-isothiocyanatophenylamino)thiocarbonyl)amino)-2-methylprop-2-yl)amino-1-hydroxyethyl)-carbostyril (HCITC) were synthesized and shown to be potent irreversible antagonist and agonist ligands, respectively, for the b-adrenoceptor in DDT 1 MF-2 (DDT) cells and the rat isolated aorta. 3 In the rat isolated aorta, DCITC (0.1 mM) did not a ect either the phenylephrine-mediated tissue contraction or the acetylcholine-mediated relaxation. DCITC attenuated the maximal (7)-isoprenalinemediated relaxation of a phenylephrine contracted aorta in a concentration-dependent manner and shifted the dose-response curves for (7)-isoprenaline to the right. The DCITC-induced decrease in maximal response was not reversed by extensive tissue washing. By use of the operational model of agonism, the calculated dissociation constant for (7)-isoprenaline ws 286 nM and the estimated receptor reserve for this agonist was 23% at the maximal response. 4 HCITC and (7)-isoprenaline stimulated cyclic AMP accumulation in DDT cells with pD 2 values (negative logarithm to base 10 of EC 50 ) of 7.95 and 7.97, respectively, and both mediated the same maximal stimulation. In the rat isolated aorta, HCITC produced a concentration-dependent relaxation of the tissue with a pD 2 value of 6.62, whereas the pD 2 for (7)-isoprenaline was 7.03. However, HCITC produced a greater maximal relaxation of the tissue than (7)-isoprenaline. The HCITC-mediated stimulation of cyclic AMP accumulation and relaxation of the isolated tissue were blocked when the bantagonist propranolol was added concurrently. In contrast, once the HCITC-mediated responses were established, the addition of propranolol did not result in any attenuation indicating that HCITC is an irreversible b-agonist.

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Chloride channels are ubiquitous proteins found in invetebrates to man. Cl- is one of the most abundant biological anions and accounts for a measurable fraction of the electrical conductance of many biological membranes. Physiologically this contributes to cellular processes, including pH regulation, volume regulation, generation of the resting membrane potential, and regulation of membrane excitability. The unitary conductance of voltage-dependent Cl- channels is as diverse as the number of different types of Cl- channels described ranging from 5-450 pS. Cl- channels are highly anion selective passing at least ten anionic species, including all of the halides. Cl- channels are blocked by various agents, including aromatic acids, inorganic cations, and protons. Maintaining high resting conductance and normal excitability, regulating cell volume, and modulating hormone action are some examples of the functions of Cl- channels. Despite the large amount of data accumulated on voltage-dependent Cl- channels, identifying subsets within this class of channels with coherent biophysical features that subserve each specific function is still not possible. At present, the molecular structure for every type of functional Cl- channels has not been determined, but future identification of cloned Cl- channel structures should provide a clearer understanding of the functional properties of background Cl- channels.