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Biomedical subjects

R Barber

Publications and source records attributed to R Barber.

At least 37 records · Page 2Linked to original sources
PubMed2000

The association between white matter lesions on magnetic resonance imaging and noncognitive symptoms.

A number of studies have suggested that cerebral changes, particularly deep white matter lesions (WML) visualized on magnetic resonance imaging (MRI), may be involved in the genesis of late life depression. This has been confirmed in a prospective study which also found a relationship between the presence of WML and poor 3-year outcome in elderly depressed subjects. Most studies find these lesions to predominate in frontal lobe and basal ganglia, supporting the hypothesis of "fronto-striatal" dysfunction in depression. To investigate whether WML are associated with mood disturbance in dementia, proton density and T2-weighted images were obtained in 80 subjects with dementia (dementia with Lewy bodies, n = 27; Alzheimer's disease, n = 28; vascular dementia, n = 25) and 26 age-matched normal controls. Periventricular lesions (PVL), white matter lesions (WML), and basal ganglia hyperintensities (BG) were visually rated blind to diagnosis using a semiquantitative scale. Frontal WML were associated with higher depression scores in patients with dementia, implying a common pathophysiology of depression irrespective of diagnosis. Further study of the neurobiological basis of WML is needed. This can best be achieved by serial clinical assessment combined with in vivo and in vitro MRI and neuropathological examination.

Aged↗
PubMed2000

Kinetic analysis of agonist-induced down-regulation of the beta(2)-adrenergic receptor in BEAS-2B cells reveals high- and low-affinity components.

We examined the interrelationships of internalization and down-regulation of the beta(2)-adrenergic receptor in response to treatment of the BEAS-2B human epithelial cell line with both a series of agonists at high occupancy and with various concentrations of fenoterol that gave occupancies from 0.93 to 0.001. We found that the extent of internalization measured after a 30-min treatment increased as a function of coupling efficiency, with ephedrine, dobutamine, albuterol, fenoterol, and epinephrine giving 0, 7, 17, 48, and 55% internalization, respectively. With the exception of dobutamine, the rates of down-regulation (k(deg)) also showed a dependence on agonist coupling efficiency, giving (in terms of fraction of receptors lost/h) 0.082 with ephedrine, 0.250 with dobutamine, 0.148 with albuterol, 0.194 with fenoterol, and 0.212 with epinephrine. Comparison of down-regulation to internalization showed that weak agonists caused down-regulation in the absence of significant internalization. The extent of internalization caused by fenoterol over a 1000-fold range of occupancy was proportional to agonist occupancy. However, although no internalization was observed with the low concentrations (0.2 and 2 nM fenoterol), these concentrations did cause significant down-regulation. Thus, as with partial agonists, it was clear that down-regulation occurred in the absence of measurable internalization. The kinetics of agonist-induced down-regulation are consistent with a scheme in which down-regulation proceeds by two pathways; a high-affinity, low-capacity component (EC(50) = 0.5 nM) clearly dissociated from internalization and a low-affinity, high-capacity component (EC(50) = 160 nM) closely correlated with internalization.

Adenylyl Cyclases↗
PubMed1999

Medial temporal lobe atrophy on MRI in dementia with Lewy bodies.

OBJECTIVE: To investigate whether medial temporal lobe atrophy (MTA) on MRI is less frequent in dementia with Lewy bodies (DLB) compared with AD and vascular dementia (VaD), and to determine the diagnostic utility of MTA in the differential diagnosis of dementia. METHOD: Coronal T1-weighted 1.0-T MR images were acquired in patients with DLB (consensus criteria; n = 26; mean age, 75.9 years), AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association; n = 28; mean age, 77.4 years), VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences; n = 24; mean age, 76.9 years), and normal control subjects (n = 26; mean age, 76.2 years). Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized scale. RESULTS: MTA was more frequent and severe in all dementia groups compared with control subjects (AD, 100%; VaD, 88%; DLB, 62%; control subjects, 4%; p < 0.001). Comparing dementia groups, MTA scores were significantly lower in DLB than AD (p = 0.002), with a trend toward less atrophy in DLB compared with VaD (p = 0.07). The absence of MTA had a specificity of 100% and 88% for separating DLB from AD and VaD respectively, and a sensitivity of 38%. In patients with DLB, MTA increased with age (r = 0.58, p = 0.002), and in all dementia patients MTA correlated with memory impairment (combined memory score, r = -0.34, p = 0.003) but not total CAMCOG score or other subscales. CONCLUSION: Patients with DLB have significantly greater MTA than control subjects but significantly less than those with AD. The authors confirmed that the presence of MTA is useful in detecting AD but less useful in differentiating between dementias. However, in the differentiation of DLB from AD and VaD, the absence of MTA is highly suggestive of a diagnosis of DLB.

Aged↗
PubMed1999

Apolipoprotein E epsilon4 allele, temporal lobe atrophy, and white matter lesions in late-life dementias.

OBJECTIVE: To examine the relationship between the apolipoprotein E (APOE) epsilon4 genotype, medial temporal lobe atrophy, and white matter hyperintensities on magnetic resonance imaging in late-life dementias. DESIGN: Structural magnetic resonance imaging study using T2-weighted and proton density-weighted axial scans and T1-weighted coronal scans. SETTING: Community-dwelling population of elderly patients prospectively chosen from a clinical case register of consecutive referrals to old age psychiatry services. SUBJECTS: Twenty-five subjects with Alzheimer disease (by criteria of the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; mean age, 77.8 years), 22 subjects with dementia with Lewy bodies (consensus criteria; mean age, 77.2 years), and 24 subjects with vascular dementia (by criteria of the National Institute of Neurological Disorders and Stroke and the Association International pour la Recherche et l'Enseignement en Neurosciences; mean age, 76.9 years) were selected. Subjects were well matched for age, sex, duration of illness, and cognitive function. MAIN OUTCOME MEASURES: The APOE genotype was determined using the polymerase chain reaction method, and medial temporal lobe atrophy and white matter hyperintensities (periventricular and deep white matter) were visually rated using standardized scales. RESULTS: In all subjects with dementia, no significant associations were noted between APOE epsilon4 status and medial temporal lobe atrophy (mean score: 0 epsilon4 = 4.5, 1 epsilon4 = 4.5, and 2 epsilon4 = 4.3; P = .90), periventricular hyperintensities (0 epsilon4 = 3.3, 1 epsilon4 = 3.1, and 2 epsilon4 = 2.9; P = .83), and white matter hyperintensities (0 epsilon4 = 5.3, 1 epsilon4 = 4.9, and 2 epsilon4 = 4.9; P = .79). CONCLUSIONS: The APOE epsilon4 allele does not determine medial temporal lobe atrophy or white matter lesions, as measured by magnetic resonance imaging in patients with Alzheimer disease, vascular dementia, or dementia with Lewy bodies. Although APOE epsilon4 may modify the risk for acquiring dementia, this finding provides further evidence that APOE epsilon4 does not influence pathological processes thereafter.

Age Factors↗
PubMed1999

Human minisatellites, repeat DNA instability and meiotic recombination.

Minisatellites include some of the most variable loci in the human genome and are superb for dissecting processes of tandem repeat DNA instability. Single DNA molecule analysis has revealed different mutation processes operating in the soma and germline. Low-level somatic instability results in simple intra-allelic rearrangements. In contrast, high frequency germline instability involves complex gene conversions and is therefore recombinational in nature, almost certainly occurring at meiosis. To determine whether true meiotic crossovers occur at human minisatellites, we have used polymorphisms near the repeat array to recover recombinant DNA molecules directly from sperm DNA. Analysis of minisatellite MS32 has revealed an intense and highly localised meiotic crossover hotspot centred upstream of the array, the first example of a human hotspot defined at the molecular level. This hotspot extends into the beginning of the repeat array, resulting in unequal and equal crossovers. Array crossovers occur much less frequently than array conversions but appear to arise by a common process, most likely by alternative processing of a recombination initiation complex. The location of MS32 at the boundary of a recombination hotspot suggests that this locus has evolved as a by-product of localised meiotic recombination activity, and that minisatellites might in general mark recombinationally proficient hotspots or hot domains in the genome. Finally, sperm crossover analysis makes it possible to explore the molecular rules that govern human meiotic recombination, and to detect phenomena such as meiotic drive that could provide a possible connection between recombination and DNA sequence diversity itself.

DNA↗
PubMed1999

Partial agonists and G protein-coupled receptor desensitization.

Weak or partial agonists induce less desensitization of G protein-coupled receptors (GPCRs) than do strong agonists. However, there have been few attempts to relate partial agonism quantitatively with the various parameters of agonist-induced desensitization, and to elucidate the mechanisms involved. Our understanding of how the treatment of cells and tissues with partial agonists affects their capacity to activate receptors is based on continued progress in defining partial agonism and the mechanisms of desensitization in which protein kinases, phosphatases, endocytosis and recycling play various roles. In this review, current research concerning partial-agonist-induced desensitization of GPCRs and the nature of partial agonism is summarized, and an attempt is made to put the existing knowledge into a working hypothesis concerning the mechanisms that account for the reduced desensitization in response to partial agonists.

Desensitization, Immunologic↗
PubMed1999

Synthesis and biodistribution of R- and S-isomers of [18F]-fluoropropranolol, a lipophilic ligand for the beta-adrenergic receptor.

The S and R isomers of [18F]-fluoropropranolol (1-[1-fluoro-2-isopropylamino]-3-naphthalen-1-yloxy-propan-2 -ol) have been prepared by reductive alkylation of the appropriate aminoalcohols. The radiosynthesis provides a reasonable yield (approximately 25%) to give products of 99% enantiomeric excess and specific activities of 1-3 Ci/micromol. The dissociation constants for the beta2 adrenergic receptor are 0.5 and 2.5 nM for the S and the R isomers, respectively. The biodistribution data in rats show that uptake and egress of the tracer is rapid but that the result of blocking studies and the difference between the R and the S isomers suggest receptor-mediated uptake in receptor-rich tissue.

Algorithms↗
PubMed1999

Neuronal accumulation of poly(ADP-ribose) after brain ischaemia.

Animal and in vitro studies suggest that overactivation of poly(ADP-ribose) polymerase (PARP) in response to oxidative DNA damage makes a substantial contribution to cell death after brain ischaemia. We have recently shown that global brain ischaemia due to cardiac arrest in man induces a rapid increase in the amount of neuronal and glial PARP that can be detected by immunohistochemistry. In the present study we sought evidence of a corresponding increase in the amount of poly(ADP-ribose) within the brain, as this would confirm PARP activation and imply resulting consumption of NAD+. We also studied the distribution of poly(ADP-ribose) accumulation in relation to morphological evidence of ischaemic damage, and used double immunolabelling to investigate the types of cell that were affected. We found that global brain ischaemia did cause accumulation of poly(ADP-ribose), particularly during the first 2 days after cardiac arrest. The distribution of cells with accumulation of poly(ADP-ribose) corresponded in general to regions of ischaemic damage or immediately adjacent neocortex. Double immunolabelling for poly(ADP-ribose) and MAP2 showed many of the cells with poly(ADP-ribose) accumulation to be neurons. Our findings are in keeping with experimental evidence of a role for PARP in post-ischaemic necrosis and of the potential for reducing ischaemic brain damage by the use of PARP inhibitors.

Adult↗
PubMed1999

Characterization of the major susceptibility region for psoriasis at chromosome 6p21.3.

Psoriasis is a common inflammatory skin condition caused by genetic and environmental factors. Recent genome-wide linkage analyses have identified a locus encoding susceptibility to psoriasis and placed this gene in the 12 cM interval between markers D6S426 and D6S276 on chromosome 6p21.3. This is a broad region and encompasses the human major histocompatibility complex. We have sought to localize the susceptibility gene more precisely by exploiting the linkage, haplotype, and linkage disequilibrium information available through genotyping 118 affected sib pairs, their parents and other affected family members. A total of 14 highly polymorphic markers were genotyped, combining anonymous loci with the class I genes HLA-B and -C distributed across a genetic interval of approximately 14 cM including the entire major histocompatibility complex. Through the application of higher density mapping within the major histocompatibility complex, we identified those regions most commonly shared identical by descent in patients with psoriasis. Using the transmission-disequilibrium test, we found significant evidence of linkage and allelic association across an interval defined by the markers tn62 (p = 1.0 x 10(-7)), HLA-B (p = 4.0 x 10(-7)), and HLA-C (p = 2.7 x 10(-9)), a region encompassed within a 285 kb genomic DNA fragment. Hence these studies contribute to the refinement of the localization of a major psoriasis susceptibility gene and place the critical region near to HLA-C.

Adolescent↗
PubMed1999

Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's disease.

Experimental studies indicate that overactivation of the DNA repair protein poly(ADP-ribose) polymerase (PARP) in response to oxidative damage to DNA can cause cell death due to depletion of NAD+. Oxidative damage to DNA and other macromolecules has been reported to be increased in the brains of patients with Alzheimer's disease. In the present study we sought evidence of PARP activation in Alzheimer's disease by immunostaining sections of frontal and temporal lobe from autopsy material of 20 patients and 10 controls, both for PARP itself and for its end-product, poly(ADP-ribose). All of the brains had previously been subjected to detailed neuropathological examination to confirm the diagnosis of Alzheimer's disease or, in the controls, to exclude Alzheimer's disease-type pathology. Double immunolabelling for poly(ADP-ribose) and microtubule-associated protein 2 (MAP2), glial fibrillary-acidic protein (GFAP), CD68, A beta-protein or tau was used to assess the identity of the cells with poly(ADP-ribose) accumulation and their relationship to plaques and neurofibrillary tangles. Both PARP- and poly(ADP-ribose)-immunolabelled cells were detected in a much higher proportion of Alzheimer's disease (20 out of 20) brains than of control brains (5 out of 10) (P = 0.0018). Double-immunolabelling for poly(ADP-ribose) and markers of neuronal, astrocytic and microglial differentiation (MAP2, GFAP and CD68, respectively) showed many of the cells containing poly(ADP-ribose) to be neurons. Most of these were small pyramidal neurons in cortical laminae 3 and 5. A few of the cells containing poly(ADP-ribose) were astrocytes. No poly(ADP-ribose) accumulation was detected in microglia. Double-immunolabelling for poly(ADP-ribose) and tau or A beta-protein indicated that the cells with accumulation of poly(ADP-ribose) did not contain tangles and relatively few occurred within plaques. Our findings indicate that there is enhanced PARP activity in Alzheimer's disease and suggest that pharmacological interventions aimed at inhibiting PARP may have a role in slowing the progression of the disease.

Aged↗
PubMed1999

White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer's disease, vascular dementia, and normal aging.

OBJECTIVES: Alzheimer's disease and vascular dementia are associated with an increase in changes in white matter on MRI. The aims were to investigate whether white matter changes also occur in dementia with Lewy bodies and to examine the relation between white matter lesions and the cognitive and non-cognitive features of dementia with Lewy bodies, Alzheimer's disease, and vascular dementia. METHODS: Proton density and T2 weighted images were obtained on a 1.0 Tesla MRI scanner in patients with dementia with Lewy bodies (consensus criteria; n=27, mean age=75.9 years), Alzheimer's disease (NINCDS/ADRDA; n=28, mean age=77.4 years), vascular dementia (NINDS/AIREN; n=25, mean age=76.8 years), and normal controls (n=26, mean age=76.2 years). Cognitive function, depressive symptoms, and psychotic features were assessed using a standardised protocol. Periventricular hyperintensities (PVHs), white matter hyperintensities (WMHs) and basal ganglia hyperintensities (BGHs) were visually rated blind to diagnosis using a semiquantitative scale. RESULTS: Periventricular hyperintensities were positively correlated with age and were more severe in all dementia groups than controls. Total deep hyperintensities scores (WMHs plus BGHs) were significantly higher in all dementia groups than controls and higher in patients with vascular dementia than those with dementia with Lewy bodies or Alzheimer's disease. In all patients with dementia, frontal WMHs were associated with higher depression scores and occipital WMHs were associated with an absence of visual hallucinations and delusions. CONCLUSION: In common with Alzheimer's disease and vascular dementia, PVHs and WMHs were significantly more extensive in dementia with Lewy bodies than in controls. This overlap between different dementias may reflect shared pathological mechanisms. The link between frontal WMHs and depression and the absence of occipital WMHs and psychotic symptoms has important implications for understanding the neurobiological basis of these symptoms.

Aged↗
PubMed1998

Apoptosis and expression of DNA repair proteins in ischaemic brain injury in man.

We examined the timing of apoptosis and the expression of the DNA repair proteins poly(ADP-ribose) polymerase (PARP) and Ku80 in sections of frontal and temporal lobes from patients who had suffered severe brain ischaemia due to a cardiac arrent. In situ end-labelling (ISEL) was used to detect apoptotic cells, and immunohistochemistry to assess PARP and Ku80. ISEL of scattered neurons and glia was demonstrable predominantly during the first 24 h after ischaemia. PARP and Ku80 immunoreactivity increased markedly after cerebral ischaemia, PARP particularly in the regions of greatest susceptibility to hypoxic injury: the CA1 field of the hippocampus and the depths of neocortical sulci. The up-regulation of PARP is in keeping with experimental observations concerning the key role of this enzyme in mediating ischaemic cell death.

Adult↗
PubMed1998

Salmeterol-induced desensitization, internalization and phosphorylation of the human beta2-adrenoceptor.

1. Partial agonists of the beta2-adrenoceptor which activate adenylyl cyclase are widely used as bronchodilators for the relief of bronchoconstriction accompanying many disease conditions, including bronchial asthma. The bronchodilator salmeterol has both a prolonged duration of action in bronchial tissue and the ability to reassert this activity following the temporary blockade of human beta2-adrenoceptors with antagonist. 2. We have compared the activation and desensitization of human beta2-adrenoceptor stimulation of adenylyl cyclase induced by salmeterol, adrenaline and salbutamol in a human lung epithelial line, BEAS-2B, expressing beta2-adrenoceptor levels of 40-70 fmol mg(-1), and in human embryonic kidney (HEK) 293 cell lines expressing 2-10 pmol mg(-1). The efficacy observed for the stimulation of adenylyl cyclase by salmeterol was only approximately 10% of that observed for adrenaline in BEAS-2B cells expressing low levels of beta2-adrenoceptor, but similar to adrenaline in HEK 293 cells expressing very high levels of receptors. Salmeterol pretreatment of these cells induced a rapid and stable activation of adenylyl cyclase activity which resisted extensive washing and beta2-adrenoceptor antagonist blockade, consistent with binding to a receptor exosite and/or to partitioning into membrane lipid. 3. The desensitization and internalization of beta2-adrenoceptors induced by the partial agonists salmeterol and salbutamol were considerably reduced relative to the action of adrenaline. Consistent with these observations, the initial rate of phosphorylation of the receptor induced by salmeterol and salbutamol was much reduced in comparison to adrenaline. 4. Our data suggest that the reduction in the rapid phase of desensitization of beta2-adrenoceptors after treatment with salmeterol or salbutamol is caused by a decrease in the rate of beta2-adrenoceptor kinase (betaARK) phosphorylation and internalization. In contrast, the rate of cyclic AMP-dependent protein kinase (PKA)-mediated phosphorylation by these partial agonists appears to be similar to adrenaline.

Adenylyl Cyclases↗
PubMed1998

Ultraviolet B induced suppression of induction of contact sensitivity in human skin is not associated with tumour necrosis factor-alpha-308 or interleukin-10 genetic polymorphisms.

Low doses of ultraviolet B (UVB) can induce localized immunosuppression in skin. This effect may be important in the induction of skin cancers and is thought to be mediated by tumour necrosis factor (TNF) alpha and interleukin (IL) 10 in conjunction with other factors. In humans a transition polymorphism in the TNF-alpha gene may affect TNF-alpha secretion and the promoter region of the IL-10 gene contains a CA repeat polymorphism which may affect gene function. We have therefore investigated the association of these polymorphisms with UVB-induced immunosuppression in humans. Volunteers (n = 42) were irradiated with UVB then sensitized on irradiated skin with diphenylcyclopropanone (DPCP) and subsequently antigen challenged with DPCP. DNA was extracted from blood samples and volunteers genotyped for the TNF-alpha polymorphism by polymerase chain reaction (PCR) and restriction digestion. The CA repeat polymorphism was amplified by PCR and sized by gel electrophoresis. Twenty-four volunteers were susceptible to UVB-induced immunosuppression and 18 were resistant. The association of allele frequencies and phenotype was statistically tested using a chi2-test. For both the TNF-alpha and IL-10 polymorphisms, there was no statistically significant association between allele types and response to UVB. These results indicate that variation in the immune response to UVB in humans is not associated with the TNF-alpha-308 transition or IL-10 CA repeat polymorphisms, although other as yet undetected DNA sequence variants of these genes may be involved.

Alleles↗
PubMed1998

Accumulation of p53 and Ki-67 expression do not predict survival in patients with fibrillary astrocytomas or the response of these tumors to radiotherapy.

OBJECTIVE: Although radiotherapy is often used in the treatment of patients with low-grade astrocytomas, its value is still uncertain. Radiotherapy carries a risk of morbidity for patients and has time and cost implications for health services. We have assessed the value of two histological variables, p53 accumulation and Ki-67 expression, in predicting the response of astrocytomas to radiotherapy. The former antigen was assessed because many astrocytic tumors show mutations in the p53 gene, the function of which is crucial for mediating cell death after radiotherapy, and the latter was assessed because it is expressed only in proliferating tumor cells, which may show greater radiosensitivity than nonproliferating cells. METHODS: Immunohistochemistry was used to detect the accumulation of p53 and expression of Ki-67 in a retrospective series of 96 patients with supratentorial fibrillary astrocytomas, 58 of whom had received postoperative radiotherapy. The immunohistochemical data were correlated with survival after radiotherapy. RESULTS: There was no significant difference in survival between the patients who did and those who did not receive radiotherapy. The p53 and Ki-67 labeling indices did not correlate with survival in either the irradiated or the nonirradiated cohort, nor with overall survival in the series as a whole. CONCLUSION: Immunohistochemical assessment of p53 accumulation and Ki-67 expression does not help in predicting the survival of patients with supratentorial fibrillary astrocytomas or in predicting whether particular patients are likely to benefit from radiotherapy.

Adolescent↗
PubMed1997

beta2-adrenergic receptor desensitization, internalization, and phosphorylation in response to full and partial agonists.

Previous studies indicated that partial agonists cause less desensitization of the beta2-adrenergic receptor (betaAR) than full agonists; however, the molecular basis for this in intact cells has not been investigated. In the present work, we have determined the rates of desensitization, internalization, and phosphorylation caused by a series of betaAR agonists displaying a 95-fold range of coupling efficiencies. These studies were performed with HEK-293 cells overexpressing the betaAR with hemagglutinin and 6-histidine epitopes introduced into the N and C termini, respectively. This modified betaAR behaved identically to the wild type receptor with regard to agonist Kd, coupling efficiency, and desensitization. The coupling efficiencies for betaAR agonist activation of adenylyl cyclase relative to epinephrine (100%) were 42% for fenoterol, 4.9% for albuterol, 2.5% for dobutamine, and 1.1% for ephedrine. At concentrations of these agonists yielding >90% receptor occupancy, the rate and extent (0-30 min) of agonist-induced desensitization of betaAR activation of adenylyl cyclase followed the same order as coupling efficiency, i.e. epinephrine >/= fenoterol > albuterol > dobutamine > ephedrine. The rate of internalization of the betaAR with respect to these agonists also followed the same order as the desensitization and exhibited a slight lag. Like internalization and desensitization, betaAR phosphorylation exhibited a dependence on agonist strength. The two strongest agonists, epinephrine and fenoterol, provoked 11-13-fold increases in the level of betaAR phosphorylation after just 1 min, whereas the weak agonists dobutamine and ephedrine caused only 3-4-fold increases, similar to levels induced by cAMP-dependent protein kinase activation with forskolin. With longer treatment times, the level of betaAR phosphorylation declined with strong agonists, but it progressively increased with the weaker partial agonists, such that after 30 min the -fold elevation with epinephrine (6.2 +/- 0.82) was not appreciably different from ephedrine (5.0 +/- 0.96) and significantly less than that caused by albuterol (10.4 +/- 1.7). In summary, our results demonstrate an excellent proportionality between the agonist strength and agonist-induced desensitization, internalization, and the rapid initial phase of phosphorylation. The data support the hypothesis that increasing agonist-coupling efficiency primarily affects desensitization by increasing the rate of betaARK phosphorylation of the betaAR.

Adenylyl Cyclases↗