The reversal of the Gpp(NH)p-activated state of adenylate cyclase by GTP and hormone is by the “collision coupling” mechanism.

Arad, Hadas; Rimon, Gilad; Levitzki, Alexander

doi:10.1016/s0021-9258(19)69846-7

Cited by 28 publications

(2 citation statements)

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“…This view is consistent with the dependence of G protein-mediated responses on the local concentration of receptors, which recalls the pattern expected if the former were determined by the integrated output of the latter (Stephenson, 1956;Furchgott, 1966). In erythrocyte membranes, for example, partial alkylation of β-adrenergic receptors has been shown to slow the rates of activation and deactivation of adenylate cyclase by agonists but not their maximal effect (Tolkovsky and Levitzki, 1978;Arad et al, 1981). In cultured L cells, both the maximal response of adenylate cyclase and the potency of epinephrine were found to vary with the level of expression of β 2adrenergic receptors (Whaley et al, 1994).…”

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confidence: 99%

“…Quantitative applications of the mobile receptor model are infrequent, but it has been reported to describe the binding of agonists to β-adrenergic receptors (De Lean et al , 1980), D 2 -dopaminergic receptors (Wreggett and De Lean, 1984), A 1 adenosine receptors (Leung et al , 1990), α 2 -adrenergic receptors (Neubig et al , 1988), and M 2 -muscarinic receptors (Ehlert, 1985, 1987; Ehlert and Rathbun, 1990; Minton and Sokolovsky, 1990). Success has been mixed, as illustrated by the common implication that guanyl nucleotides such as GMP-PNP cause an irreversible loss of G proteins from the system. Owing to this and other anomalies, the model has not provided a mechanistically consistent description of the binding patterns and the changes effected by guanyl nucleotides (Wong et al , 1986; Lee et al , 1986).…”

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Cardiac Muscarinic Receptors. Relationship between the G Protein and Multiple States of Affinity

1997

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An expanded version of the mobile receptor model has been assessed in studies on the binding of N-[3H]methylscopolamine and [35S]GTPgammaS to cardiac muscarinic receptors and their attendant G proteins in ventricular membranes from hamster. The model comprises two pools of receptor, one of which lacks G proteins, and a heterogeneous population of G proteins that compete for the receptor within the G protein-containing pool. To guide the formulation of the model itself and to define the various parameters, data were combined from assays performed under various conditions with native membranes and following irreversible blockade of about 80% of the receptors with propylbenzilylcholine mustard. Multiple G proteins are indicated primarily by multiple states of affinity evident in the dose-dependent effect of guanyl nucleotides on the binding of carbachol; G protein-free receptors are indicated by sites of low affinity for carbachol that survive treatment with the mustard. The expanded model generally succeeds where more frugal schemes have been inadequate, but it nevertheless fails to yield a mechanistically consistent description of the data. Guanyl nucleotides and partial alkylation do not affect the inhibitory potency of carbachol in a manner consistent with their supposed effect on the equilibrium between uncoupled and G protein-coupled receptors. As inferred from the model, G proteins are lost upon alkylation of the receptor, and their numbers are regulated by guanyl nucleotides. Parameters estimated via N-[3H]methylscopolamine are wholly inconsistent with the same parameters estimated via [35S]GTPgammaS. The failure of the model suggests that multiple states of affinity may not arise from a ligand-regulated equilibrium between free receptors and G proteins on the one hand and one or more RG complexes on the other.

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Cardiac Muscarinic Receptors. Relationship between the G Protein and Multiple States of Affinity

1997

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Reconstitution of beta-adrenergic receptor with components of adenylate cyclase.

Hekman¹,

D²,

Keenan³

et al. 1984

The EMBO Journal

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Beta 1‐Adrenergic receptor proteins were extracted from turkey erythrocyte membranes with lauroyl sucrose and digitonin and purified by affinity chromatography on a column of alprenolol agarose Affi‐gel 10 or 15. The 5000‐fold purified receptor is able to couple functionally with the stimulatory GTP‐binding protein (GS) from either turkey or duck erythrocytes. Functional coupling was achieved by three different approaches. (i) Purified beta‐receptor polypeptides were coupled in phospholipid (asolectin) vesicles with GS from a crude cholate or lauroyl sucrose extract of turkey erythrocyte membranes. The detergent was removed and vesicles were formed with SM‐2 beads. (ii) Purified beta‐receptor was reconstituted with pure, homogeneous GS in asolectin vesicles. (iii) Purified beta‐receptors were either coupled in asolectin vesicles with a mixture of pure, homogeneous Gpp(NH)p‐activated GS and a lauroyl sucrose extract of turkey erythrocyte membranes, or with pure, homogeneous Gpp(NH)p‐activated GS alone. The decay of activity was measured on addition of GTP and hormone. In (ii) and (iii), the detergent was removed and vesicles were formed by gel filtration on Sephadex G‐50 columns. In each of the three different experimental conditions, the beta‐receptor was activated with l‐isoproterenol and activation was blocked with d,l‐propranolol. Activated GS were measured separately by means of their capacity to activate a crude Lubrol PX‐solubilized adenylate cyclase preparation from rabbit myocardial membrane. The kinetics of GS activation by purified beta‐receptors occupied by l‐isoproterenol was first order and activation was linearly dependent on receptor concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

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Signal Transduction in the β-Adrenoceptor-Dependent Adenylate Cyclase

Levitzki¹

1988

Enzyme Dynamics and Regulation

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The reversal of the Gpp(NH)p-activated state of adenylate cyclase by GTP and hormone is by the “collision coupling” mechanism.

Cited by 28 publications

References 20 publications

Cardiac Muscarinic Receptors. Relationship between the G Protein and Multiple States of Affinity

Cardiac Muscarinic Receptors. Relationship between the G Protein and Multiple States of Affinity

Reconstitution of beta-adrenergic receptor with components of adenylate cyclase.

Signal Transduction in the β-Adrenoceptor-Dependent Adenylate Cyclase

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