INDEX

Acid-resistant binding,

indicator of internalization, 190-191

Adair, G. S., 92, 124-129

Adair model, 124-126

Adair's equation, 127-129

Adsorption to filters, 80, 176-177

Agonist drug, defined, 1

Ahlquist, R. P., 30-31

Allosteric modulation, 115-117

analyzed by a Three-State Model, 22-23

determination using kinetic strategies, 115-117

Allosteric theory, 19-21

212 Cell Surface Receptors

Ammonium sulfate, 114, 175-176

Ariens, E. J., 9-12, 16, 18,45

Association rate constant, 17, 66, 69, 74, 107-113

determination of, 107-113

Bernard, C , 3, 6

Biological detergents, 157-179

choice of, 167-169

Black and Leff, 14-15,24

Caveoli, 184

Centrifugation,

to terminate binding assay, 72-73

Chemotherapeutic index, 5

Cheng and Prusoff/Chou equation, 97-99, 103-105, 134

Clark, A. J., 7-16, 24, 37, 77

Clathrin-coated pits, 183-184, 204

Colquhoun, D., 20, 44, 55, 150

Colo wick and Womack procedure, 71-72

disadvantages, 71

use in association experiments, 71

Competition binding data,

analysis by non-linear regression, 134-138

Competition binding studies, 95-102, 117, 123, 131-141, 148

Lee E. Limbird, Ph.D. 213

position of curve, 101

shape of curve, 100-102

Complex binding phenomena,86, 93, 95, 123-153

analysis by non-linear regression, 131-139

Computer-assisted analysis,

linear regression, 41, 48, 53-54, 60

non-linear regression, 80, 85-95, 98, 123-124, 131-139

Constitutively active receptors, 49, 56, 149-151

Critical micelle concentration (cmc), 160-163, 166-169

Cross-desensitization, 34

Cross-protection, 33-34

Detergents, 157-179

Dissociation profiles,

determination of koff, 115, 149

use to reveal allosteric effect, 115-117

use to reveal negative or positive cooperativity, 113-115

Dissociation rate constant, 18, 66, 70, 102, 107, 110-113

determination of, 110-113

Drug, defined, 1

Efficacy, 2, 11-15, 18-19, 22-23, 27, 30, 37-40, 43-49, 55, 96, 145, 147, 150

Endocytosis, 183-184, 190-191, 194-195, 199,201-206

endocytotic rate constant determination, 201-206

214 Cell Surface Receptors

Equilibrium association constant, 31, 36-60, 68, 71, 74-103, 106-117,

123, 132, 134, 137-141, 149, 152, 179, 196-197, 205

measurement of, 107-110

Equilibrium dialysis, 69-72, 171, 173

Erhlich, P., 4-7

Floating receptor model, 147

Furchgott, R. F., 10, 12-16, 30, 33

Gaddum, J. H., 8, 13, 50, 58, 61

Gel filtration, 168, 173-175

Ghost sites, 131

Heavy amino acid techniques, 204-206

Hill, A. v., 19, 124

Hill coefficient (nw), 93-96, 101, 123, 131, 133

pseudo-, 101

Hill plot, 80, 92-95, 97-98, 131-133

indirect, 97-98, 133

Hummel-Dreyer chromatographic procedure, 171-173

Hyperbolic relationship of mass action law, 78

Impermeant ligands, 185-189

Insertion of receptors, 192, 195-206

rate determination, 195-204

Intact cell binding, 83, 188, 195-204

Lee E. Limbird, Ph.D. 215

steady state model for characterization, 195-204

Integral membrane proteins, 159-162, 167, 169

Internalization of receptors, 83, 184-185, 188, 191-203

acid-resistant binding as indicator, 190-191

impermeant ligands, 185-189

protease-resistant binding, 189-190

Intrinsic activity, 10-12, 16, 49, 56, 144, 149-150

Intrinsic efficacy (G ), 39, 43

Inverse agonist drug, defined, 1

KD values,

estimated, using radioligand binding assays, 76-79, 85-87

estimated, using response data,

for agonists, 37-44

for antagonists, 49-55

for partial agonists, 44-49

for inverse agonists, 55-56

Kenakin, T. P., 2, 21-22, 30, 47-49, 53-58, 104-106, 149-153

Klotz, L, 85-86, 90, 128-131

Langley, J. N., 4, 6-7

Langmuir binding isotherm, 128

Langmuir isotherms, 7, 77, 128

216 Cell Surface Receptors

Ligand, impermeant, 185-189

Lineweaver-Burk (double reciprocal) plots/analysis, 13, 86

Membrane proteins, 67, 90, 159-163, 167

integral, 159-162, 167, 169

peripheral, 159

Micelle, 157, 169, 173-174

Michaelis-Menten, 77, 100, 128

Negative antagonists (inverse agonists), 1-2, 22-23, 29, 31, 37, 49, 55-56, 61

Negative cooperativity, 53, 81, 91, 94, 100, 105, 113-115, 128, 130-132, 133,

139

elucidation with kinetic strategies, 95, 106, 115-117, 132

UH (Hill coefficient), 93-96, 101, 123, 131, 133

pseudo-, 101

Nickerson, M., 13-14

Nonspecific binding, 73, 80-85, 96, 98, 133-137, 173, 176

approaches to defining, 80-82

"Null" antagonists, 2, 31, 49-51, 55, 59-61, 96, 144, 147

Occupancy theory, 7-12, 17-19

Operational models of agonism, 14-21

Partial agonists/agonism, 1-2, 12-16, 20, 23-25, 29-31, 37, 44-49, 51, 144

Paton, W. D. M., 17-19,56,59

Peripheral membrane proteins, 159

Lee E. Limbird, Ph.D. 217

Polyethylene glycol (PEG), 175-176

Polyethyleneimine (PEI), 176

Precipitation of solubilized receptors, 165, 169, 175-176, 190, 201

Protease-resistant binding, 189-190

indication of receptor internalization, 190

Protection against irreversible receptor blockade, 32-45

Radioligand, 23, 43-44, 61-62, 65-87, 95, 99-124, 131-135

selection, 66-67

Rate theory, 17-19

Receptor,

development of concept, 2-7

spare receptors, 13-14, 30, 34, 48

Receptor affinity states, 86, 91, 94, 112-113, 118, 124, 131, 133-134, 139,

143-146, 148-149, 152-153

Receptor identification criteria, 65-66, 179, 183, 195

Receptor immobilization, 177-179

Receptor recycling, 183-184, 191-195,204

Receptor subtypes, 31, 55, 139-144, 152, 188

analysis of, 140-142

a-adrenergic as example, 188

p-adrenergic as example, 188

Rectangular hyperbolic relationship of ligand binding, 14-16, 78-79, 85

218 Cell Surface Receptors

Recycling of receptors, 183-184, 191-195, 204

Resultant analysis, 42, 56-58

Rosenthal plot, 89-92, 99

derivation, 89-90

Saturability of radioligand binding, 75-80

Saturation binding data, 82-95, 134-135

Scatchard, G., 87-89

Scatchard plots, 86-88, 90-91, 117, 123, 131, 197

interpretation of, 86-88, 90-91

Schild,H.O., 51-52

Schild analysis, 49

Schild plot, 52-55, 60

Schild regression, 53

Solubilized receptors, 157, 167, 170-180

analysis, 171-179

operational criteria for, 170

Spare receptors, 13-14, 30, 34, 48

Specific radioactivity, 67

impact on sensitivity for receptor detection, 67, 83

isotopes, 66-67

Specificity, assessing receptor, 29-35, 61, 95-96

blockade by antagonist agents, 31

Lee E. Limbird, Ph.D. 219

competition binding curves, 101-103

cross-desensitization, 34

order of agonist potency, 30

order of antagonist potency, 31

protection against irreversible receptor blockade, 32

Steady state (vs. equilibrium), 19, 31, 71-72, 75, 82, 91, 95, 98, 101, 111,

114-115, 195

Steady state model for analyzing binding data to intact cells, 195-204

steady state binding constant, K^s, 197, 199, 201-202

Stephenson, R., 9-12, 16, 18, 24, 37, 39-40, 44, 47

Subtypes of receptors, 31, 55, 139-144, 152, 188

analysis of, 140-143

Ternary complex model, 16, 43-44, 56, 105, 131, 145-153

Three-State Model(s), 22

Thermodynamic parameters, 97

Transducer ratio, x (tau), 15, 17, 24

Two-State Model(s), 21-23

Vacuum filtration, 69, 71, 73-74, 148, 171, 175-176

Van Rossum, J. M., 12, 45