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Biomedical subjects

Helmut Schröder

Publications and source records attributed to Helmut Schröder.

At least 19 recordsLinked to original sources
PubMed2007

Moderate consumption of olive oil by healthy European men reduces systolic blood pressure in non-Mediterranean participants.

We evaluated the effects of a moderate consumption of olive oil on lipid profile, BMI, and blood pressure (BP) in a group of 160 healthy men from non-Mediterranean regions [Northern Europe (n = 50; Finland and Denmark) and Central Europe (n = 60; Germany)] and Mediterranean regions [Southern Europe (n = 45; Italy and Spain)]. The study was a randomized, cross-over trial with 3 intervention periods of 3 wk and 2 wash-out periods of 2 wk. At the intervention periods, 3 similar olive oils (25 mL/d), differing only in their phenolic concentration, were administered to the healthy volunteers. Plasma oleic acid levels increased 2-3% (P < 0.05) in men from populations with lower habitual olive oil intakes (Northern and Central Europe). General linear models showed that the administration of the sequence of the 3 olive oils was responsible for a 3% decrease in systolic BP (SBP) (P < 0.05), but not in diastolic BP, in the non-Mediterranean subjects. Multivariate analysis indicated that the lipid profile did not change in either Mediterranean or non-Mediterranean men due to the olive oil intervention. The results of this study suggest that a moderate consumption of olive oil may be used as an effective tool to reduce SBP of healthy men who do not typically consume a Mediterranean diet. However, additional longer trials are necessary for confirmation.

Adult↗
PubMed2006

Myocardial infarction and alcohol consumption: a population-based case-control study.

BACKGROUND AND AIM: Coronary heart disease (CHD) is the leading cause of death in industrialized societies. Identifying and characterizing modifiable variables associated with CHD is an important issue for health policy. The aim of the present study was to analyze the association of non-fatal myocardial infarction with total alcohol consumption and type of alcoholic beverage consumed. Preference of the subjects' consumption for beer, wine, or spirits was set at 80% or more of total alcoholic beverage consumption. METHODS AND RESULTS: A population-based case-control study (244 subjects and 1270 controls) was conducted. Male patients aged 25 to 74 years with first myocardial infarction (MI) were recruited in the same region as the healthy male controls, who were taken from a random sample representative of the Gerona population. Alcoholic beverage consumption during the preceding week was recorded. Multiple logistic regression analysis was performed to determine the association of alcohol consumption and non-fatal MI. Total alcohol consumption up to 30 g per day, adjusted for lifestyle and cardiovascular risk factors, was inversely associated (Odds ratio 0.14; 95% confidence interval 0.06-0.36) with the risk of non-fatal MI. Drinking up to 20 g of alcohol through wine, beer and spirits significantly decreased the adjusted risk of MI. Higher alcohol intake did not substantially reduce the risk. A preference for spirits was correlated with a significantly increased risk of non-fatal MI (P<0.05). CONCLUSION: Moderate alcohol consumption, independent of the type of alcoholic beverage, was associated with non-fatal MI risk reduction.

Adult↗
PubMed2006

Pain sensitivity is altered in animals after subchronic ketamine treatment.

RATIONALE: Clinical observations have shown that pain sensitivity is altered in some schizophrenic patients. OBJECTIVES: To study alterations in pain sensitivity, the ketamine model in schizophrenia research was employed. MATERIALS AND METHODS: Rats were subchronically injected with the dissociative anaesthetic ketamine (Ket, ten injections of 30 mg/kg, one injection per day over a period of 10 days). Two weeks after treatment completion, the animals' pain sensitivity was assayed in the hot plate test and they were subjected to electrical stimulation of the tail root. In addition, the effect of morphine was studied. RESULTS: In group-housed animals, there was no difference between Ket-injected animals and control rats as measured in both nociceptive tests. In singly housed Ket-injected rats, pain threshold was increased in the electrical stimulation test. This suggests that stress due to single housing might be essential for modifications of pain sensitivity. Moreover, the antinociceptive effect of morphine was modified after single housing. Interestingly, the effect of morphine on locomotor activity was similar in both groups. In group-housed rats, mu receptor binding was unchanged in the frontal cortex, whereas Ket-injected animals had decreased levels in the hippocampus. In singly housed animals, mu receptor binding in Ket-injected rats increased in the frontal cortex and decreased in the hippocampus. (35)S-GTPgamma-S binding increased in the frontal cortex in both singly housed groups, but remained unchanged in the hippocampus. CONCLUSIONS: The data suggest that the ketamine model might be useful for studying altered pain sensitivity in schizophrenia. Moreover, the data suggest that modifications in mu opioid receptor binding contribute to this phenomenon.

Analgesics↗
PubMed2006

Protective mechanisms of the Mediterranean diet in obesity and type 2 diabetes.

The prevalence of obesity has grown to an alarming level of at least 300 million people worldwide. Additionally, a diabetes epidemic is underway, with an estimate of 217 million people with diabetes worldwide. There are many links between excessive body weight and type 2 diabetes, and one common and fundamental cause of both epidemics is an unhealthy diet. Research to identify and promote diets that protect individuals from obesity and type 2 diabetes is urgently needed. The Mediterranean diet, a concept developed in the 1950s, refers to dietary habits of individuals from the Mediterranean basin. The Mediterranean diet is an eating pattern that successfully combines pleasant taste and positive health effects. The Mediterranean diet does not stand for a homogenous and exclusive model among the Mediterranean basin population but rather represents a set of healthy dietary habits, including high consumption of vegetables and fresh fruits and the use of olive oil as the main source of fat. Evidence from epidemiological studies supports a protective effect of this dietary pattern on weight gain and the development of type 2 diabetes. Several mechanistic explanations link characteristic components of the Mediterranean diet with obesity and type 2 diabetes. This review will discuss potential mechanisms by which the Mediterranean diet protects individuals from both diseases.

Alcohol Drinking↗
PubMed2006

Circulating oxidized LDL is associated with increased waist circumference independent of body mass index in men and women.

BACKGROUND: Obesity is associated with oxidative stress, and the oxidation of LDL is thought to play a crucial role in the generation of atherosclerotic lesions. OBJECTIVE: The objective was to describe the association of waist circumference (WC) and body mass index (BMI; in kg/m2) with plasma circulating oxidized LDL (ox-LDL) and C-reactive protein (CRP). DESIGN: This cross-sectional study included data for circulating ox-LDL and CRP from a subpopulation of 586 men and women enrolled in a population-based survey conducted in 2000 in Girona, Spain. Multivariate analysis was performed to describe the independent association of WC and BMI with ox-LDL and CRP. RESULTS: Multivariate logistic regression analysis adjusted for lifestyle, educational level, and dietary confounders showed a direct association of WC (quartile distribution) and BMI categories with ox-LDL (P for linear trend = 0.002) and CRP (P for linear trend = 0.004). Subjects in the top quartile of WC and with a BMI > 29.9 were at high risk of elevated circulating concentrations of ox-LDL and CRP. Further adjustment for cardiovascular disease risk factors did not substantially modify these associations. The risk of high ox-LDL concentrations in overweight (BMI = 25.0-29.9) or obese (BMI > or = 30) subjects with a WC < 102 cm (men) or < 88 cm (women) was not significantly different from that in normal-weight subjects with these WCs. In contrast, overweight or obese subjects with higher WCs (WC > or = 102 cm for men and > or = 88 cm for women) were at significantly higher risk of increased ox-LDL. CONCLUSION: High WC was associated with high concentrations of ox-LDL independently of BMI in the study population.

Abdominal Fat↗
PubMed2006

Prescription practice for LH-RH analogs and androgen receptor antagonists in the treatment of advanced prostate cancer in Germany (1993-2003).

INTRODUCTION: Nearly 80% of the patients suffering from advanced stages of prostate cancer in Germany are treated currently with luteinizing hormone-releasing hormone (LH-RH) analogs alone or in combination with androgen receptor antagonists. The aim of this study was to assess whether the prescription practice for LH-RH analogs and direct antiandrogens between 1993 and 2003 parallels the rise in the incidence rates for prostate cancer associated with the proportional rise in daily doses. METHODS: Between 1993 and 2000 a yearly randomly selected number of receipts has been evaluated from official pharmacies in Germany which have been billed to public health insurance companies. Data concerning drug use, number of daily doses, and total cost of the respective drugs have been calculated by the Research Institute of the AOK (Wissenschaftliches Institut der AOK, WIdO). These prescription data have been related to incidence and mortality rates of patients with prostate cancer. RESULTS: Between 1993 and 2003 the age-standardized incidence rate of carcinomas of the prostate has risen by 180%, while the disease-specific mortality practically has remained nearly at the same level. The daily prescribed doses of LH-RH analogs have risen by a factor of 8.5 from 3.9 to 33.5 million daily doses during this time. In contrast, the daily doses of androgen receptor antagonists have remained unchanged between 1997 and 2001, followed by a rise of 50% between 2001 and 2003. CONCLUSIONS: The first analysis of the prescription practice of antiandrogens in the treatment of prostate cancer with respect to the incidence rates in Germany could only be facilitated by the fact that these medications are in exclusive use for this indication in Germany. The rise in prescriptions may be explained by the therapy shift from surgery to LH-RH application until the year 2000; the reasons for a further rise since 2000 remain speculative. In conclusion, only prevalence data would allow the exact calculation of medication needs among prostate cancer patients.

Aged↗
PubMed2005

Cardiovascular risk profile and type of alcohol beverage consumption: a population-based study.

AIMS: To determine the association between several cardiovascular risk factors with total alcohol and types of alcoholic beverage consumption. METHODS: The subjects were Spanish men (n = 2,383) and women (n = 2,535) aged 25-74 years who were examined in 1994-1995 and 1999-2000, in two population-based cross-sectional surveys in the north-east of Spain (Gerona). Information of total amount and type of alcohol consumption, educational level, smoking, leisure-time physical, antihypertensive and hyperlipidemic drug treatment was obtained through structured questionnaires. The cardiovascular risk factors total cholesterol, HDL cholesterol, triglycerides, fasting glucose, fibrinogen, lipoprotein (a), heart rate and systolic and diastolic blood pressures were determined. RESULTS: Men consumed significantly more alcohol than women (19.5 vs. 4.5 g/day, respectively) and the prevalence of elevated alcohol consumption (>2 glasses of wine/day) also was higher in men (35.3%) than women (3.5%). Total alcohol intake was significantly related with HDL cholesterol and fibrinogen improvements in both genders. In contrast, total cholesterol, triglycerides, heart rate, and systolic and diastolic blood pressures were directly and significantly (p < 0.05) associated with total alcohol consumption in men but not in women. Wine drinking, particularly in women, was associated with a healthy cardiovascular risk profile. Most of the observed significant associations between type of alcohol beverage and CHD risk factors disappeared after controlling for total alcohol consumption and other confounders. CONCLUSIONS: Alcohol consumption was favorably related to the cardiovascular risk profile in women but not in men. The relationship of alcohol beverages seems to be mediated by the total alcohol content rather than by the type of beverage itself.

Alcohol Drinking↗
PubMed2004

Transcriptional regulation of the human mu-opioid receptor gene by interleukin-6.

Inflammatory pain is counteracted by a number of physiological processes. For example, opioid receptors, which are present on peripheral terminals of sensory neurons, are activated by endogenous opioids, which are released from immune cells migrating to the inflamed tissue. Earlier data demonstrated that interleukin-6 contributes to such inflammation-induced analgesia. In this report, we demonstrated that interleukin-6 strongly induces mu-opioid receptor mRNA in the human neuroblastoma cell line SH SY5Y, whereas delta-opioid receptor mRNA levels are not influenced. The mRNA increase in these cells is followed by an increase in mu-opioid receptor-specific binding. Using transcription factor decoy oligonucleotides, direct evidence was provided that the up-regulation of mu-opioid receptor mRNA in intact cells is dependent on the transcription factors signal transducers and activators of transcription 1 (STAT1) and STAT3, whereas other transcription factors, such as activator protein-1, nuclear factor (NF)-kappaB, or NF-interleukin-6 are not involved. STAT1 and STAT3 bound to a site located at nucleotide -1583 on the promoter of the human mu-opioid receptor gene, as shown by transient transfection experiments, electrophoretic mobility shift assays, and transcription factor decoy oligonucleotides. A mutation analysis of the 5'-TTCATGGAA-3' STAT1/3 element (palindrome underlined) was performed to determine nucleotide residues that are necessary for the binding of STAT1 and STAT3. It suggested that only the palindromic half sides and the two adjacent central nucleotides are required. Neither mutation of the nucleotides outside the palindrome nor mutation of the central nucleotide affected STAT1/3 binding.

Base Sequence↗
PubMed2004

Risk assessment of the potential side effects of long-term creatine supplementation in team sport athletes.

BACKGROUND: Use of creatine has become widespread among sportsmen and women, although there are no conclusive evidences concerning possible health risks of long-term creatine supplementation. THE AIM OF THE STUDY: To investigate long-term effects of creatine monohydrate supplementation on clinical parameters related to health. METHODS: Eighteen professional basketball players of the first Spanish Basketball League participated in the present longitudinal study. The subjects were ingesting 5 g creatine monohydrate daily during three competition seasons. Blood was collected in the morning after an overnight fast, five times during each of the three official competition seasons of the first National Basketball League (September 1999-June 2000, September 2000-June 2001 and September 2001-June 2002) and the European League. Standard clinical examination was performed for 16 blood chemistries. RESULTS: The plasma concentrations of all clinical parameters did not alter significantly during the analyzed time frames of creatine supplementation. All of these parameters were, with the exception of creatinine and creatine kinase, within their respective clinical ranges at all time points. CONCLUSION: Our data shows that low-dose supplementation with creatine monohydrate did not produce laboratory abnormalities for the majority of the parameters tested.

Adult↗
PubMed2004

Relationship of socioeconomic status with cardiovascular risk factors and lifestyle in a Mediterranean population.

BACKGROUND: Socioeconomic status greatly affects cardiovascular risk factors and lifestyle. Aim of the study To analyse the relationship between socioeconomic status and both cardiovascular risk factors and behavioural variables. AIM OF THE STUDY: To analyse the relationship between socioeconomic status and both cardiovascular risk factors and behavioural variables. METHODS: The present random sample of 838 men and 910 women of the 25 to 74 year old general population of Gerona according to the 1991 census, included cardiovascular risk factor measurements (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glycaemia, systolic blood pressure, diastolic blood pressure, body mass index, waist to hip ratio, and waist circumferences) and evaluation of dietary habits, alcohol consumption, smoking, and leisure-time physical activity with corresponding questionnaires. RESULTS: In this study, we used lifestyle factors (leisure-time physical activity, tobacco consumption, and alcohol drinking habits) in addition to dietary habits to determine whether changes in these factors correlate with the socioeconomic status, classified as degree of educational level, in a representative Spanish Mediterranean population. Multiple linear regression analysis adjusted for several confounders revealed a direct association of LDL-cholesterol (p = 0.03) and body mass index (p = 0.02) with low levels of educational status in men and women, respectively. A higher educational status was directly (p = 0.04) related to the smoking status in women. The two composite dietary scores, indicating overall dietary quality and cardiovascular protecting properties, were not associated with low socioeconomic status in our population. CONCLUSION: Dietary habits, alcohol drinking, and leisure-time physical activity seems not to be affected by educational status in either gender. This finding might partially explain the relationship between cardiovascular risk factors and socioeconomic status in our population. The importance of cultural values in the rural area of the Spanish province seems to be the stronger factor compared with education.

Adult↗
PubMed2004

Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation--a randomized controlled trial.

BACKGROUND: Evidence from in vitro studies suggests that antioxidant olive oil phenolic compounds can prevent LDL oxidation. However, in vivo evidence in support of this hypothesis is sparse. AIM OF THE STUDY: to establish the antioxidant effect of olive oils with differences in their phenolic compounds content in humans METHODS: A controlled, double blind, cross-over, randomized, clinical trial using three similar olive oils with increasing phenolic concentration (from 0 to 150 mg/Kg) was conducted in 30 healthy volunteers. Olive oils were administered over three periods of 3 weeks preceded by two-week washout periods. RESULTS: Urinary tyrosol and hydroxytyrosol increased (p < 0.020), in vivo plasma oxidized LDL decreased (p = 0.006), and ex vivo resistance of LDL to oxidation increased (p = 0.012) with the phenolic content of the olive oil administered. After virgin olive oil administration, an increase (p = 0.029) was observed in HDL cholesterol levels. CONCLUSIONS: Sustained consumption of virgin olive oil with the high phenolic content was more effective in protecting LDL from oxidation and in rising HDL cholesterol levels than that of other type of olive oils. Dose-dependent changes in oxidative stress markers, and phenolic compounds in urine, were observed with the phenolic content of the olive oil administered. Our results support the hypothesis that virgin olive oil consumption could provide benefits in the prevention of oxidative processes.

Antioxidants↗
PubMed2004

Phospholipase D2 modulates agonist-induced mu-opioid receptor desensitization and resensitization.

Receptor phosphorylation, arrestin binding, uncoupling from G protein and subsequent endocytosis have been implicated in G protein-coupled receptor desensitization after chronic agonist exposure. In search of proteins regulating the mu-opioid receptor endocytosis, we have recently established that activation of phospholipase D (PLD)2 is required for agonist-induced mu-opioid receptor endocytosis. In this study, we determined the effect of PLD2 activity on the desensitization and resensitization rate of the mu-opioid receptor. We clearly demonstrated that inhibition of PLD2-mediated phosphatidic acid formation by alcohol (1-butanol or ethanol) or overexpression of a dominant negative mutant of PLD2 prevented agonist-mediated endocytosis and resulted in a faster desensitization rate of the mu-opioid receptor after chronic (D-Ala2, Me Phe4, Glyol5)enkephalin treatment in human embryonic kidney 293 cells. Moreover, inhibition of PLD2 activity led to an impairment of the resensitization rate of the mu-opioid receptor. In summary, our data strongly suggest that PLD2 is a modulator of agonist-induced endocytosis, desensitization and resensitization of the mu-opioid receptor.

1-Butanol↗
PubMed2004

Adherence to the traditional mediterranean diet is inversely associated with body mass index and obesity in a spanish population.

The Mediterranean diet is a healthy eating pattern with protective effects on chronic diseases. The purpose of this study was to assess the relation between BMI and obesity and the level of adherence to the traditional Mediterranean diet. The subjects were Spanish men (n = 1547) and women (n = 1615) aged 25-74 y who were examined in 1999-2000, in a population-based, cross-sectional survey in the northeast of Spain (Girona). Dietary intake was assessed using a FFQ. A Mediterranean diet score, including foods considered to be characteristic components of the traditional Mediterranean diet (vegetables, fruits, pulses, nuts, fish, meat, cereals, olive oil, and wine) was created. An increase of 5 U in the dietary score was associated with a change in the BMI of 0.43 (P = 0.030) and 0.68 (P = 0.007), after controlling for potential confounders, in men and women, respectively. The obesity risk decreased in men (P = 0.010) and women (P = 0.013) with increasing adherence to the traditional Mediterranean dietary pattern. The population in the top tertile of this score were less likely to be obese in both genders [odds ratio (OR) and (95% CI): 0.61 (0.40-0.92) in men; 0.61 (0.40-0.93) in women] after adjusting for potential confounders. These data suggest that the traditional Mediterranean dietary pattern is inversely associated with BMI and obesity. This finding may be useful in the development of dietary approaches for dietary counseling and the prevention of obesity.

Adult↗
PubMed2004

Effect of the A118G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization, and resensitization of the human mu-opioid receptor.

The most prevalent single-nucleotide polymorphism (SNP) A118G in the human mu-opioid receptor gene predicts an amino acid change from an asparagine residue to an aspartatic residue in amino acid position 40. This N40D mutation, which has been implicated in the development of opioid addiction, was previously reported to result in an increased beta-endorphin binding affinity and a decreased potency of morphine-6-glucuronide. Therefore, in the present study we have investigated whether this mutation might affect the binding affinity, potency, and/or the agonist-induced desensitization, internalization and resensitization of the human mu-opioid receptor stably expressed in human embryonic kidney 293 cells. With the exception of a reduced expression level of N40D compared to human mu-opioid receptor (hMOR) in HEK293 cells, our analyses revealed no marked functional differences between N40D and wild-type receptor. Morphine, morphine-6-glucuronide and beta-endorphin revealed similar binding affinities and potencies for both receptors. Both the N40D-variant receptor and hMOR exhibited robust receptor internalization in the presence of the opioid peptide [d-Ala(2),N-MePhe(4),Glyol(5)]enkephalin (DAMGO) and beta-endorphin but not in response to morphine or morphine-6-glucuronide. After prolonged treatment with morphine, morphine-6-glucuronide or beta-endorphin both receptors showed similiar desensitization time courses. In addition, the receptor resensitization rates were nearly identical for both receptor types.

Amino Acid Substitution↗
PubMed2003

Heterodimerization of substance P and mu-opioid receptors regulates receptor trafficking and resensitization.

The micro-opioid receptor (MOR1) and the substance P receptor (NK1) coexist and functionally interact in nociceptive brain regions; however, a molecular basis for this interaction has not been established. Using coimmunoprecipitation and bioluminescence resonance energy transfer (BRET), we show that MOR1 and NK1 can form heterodimers in HEK 293 cells coexpressing the two receptors. Although NK1-MOR1 heterodimerization did not substantially change the ligand binding and signaling properties of these receptors, it dramatically altered their internalization and resensitization profile. Exposure of the NK1-MOR1 heterodimer to the MOR1-selective ligand [D-Ala2,Me-Phe4,Gly5-ol]enkephalin (DAMGO) promoted cross-phosphorylation and cointernalization of the NK1 receptor. Conversely, exposure of the NK1-MOR1 heterodimer to the NK1-selective ligand substance P (SP) promoted cross-phosphorylation and cointernalization of the MOR1 receptor. In cells expressing MOR1 alone, beta-arrestin directs the receptors to clathrin-coated pits, but does not internalize with the receptor. In cells expressing NK1 alone, beta-arrestin internalizes with the receptor into endosomes. Interestingly, in cells coexpressing MOR1 and NK1 both DAMGO and SP induced the recruitment of beta-arrestin to the plasma membrane and cointernalization of NK1-MOR1 heterodimers with beta-arrestin into the same endosomal compartment. Consequently, resensitization of MOR1-dependent receptor functions was severely delayed in coexpressing cells as compared with cells expressing MOR1 alone. Together, our findings indicate that MOR1 by virtue of its physical interaction with NK1 is sequestered via an endocytotic pathway with delayed recycling and resensitization kinetics.

Arrestins↗
PubMed2003

Relationship between body mass index, serum cholesterol, leisure-time physical activity, and diet in a Mediterranean Southern-Europe population.

The aim of the present study was to determine the relationship of BMI with other cardiovascular risk factors, leisure-time physical activity and diet. Participants were recruited in a cross-sectional population-based survey in a southern-Europe Mediterranean population (Spain); cardiovascular risk factors were measured, and leisure-time physical activity and diet intake were evaluated. Linear regression analysis adjusted for several confounders showed a significant, direct association of BMI and total cholesterol (P<0.005) and LDL-cholesterol (P<0.006), in men. HDL-cholesterol was inversely related to BMI in both sexes (P<0.0001). Higher BMI was more frequent in less-active men (P<0.04) but not in women. BMI increased significantly (P<0.0001) by 1.92 kg/m(2) with each 4.18 MJ consumed in men but not in women. Dietary intakes of carbohydrate (P<0.03), total fat (P<0.03) and saturated fatty acids (P<0.02) were directly associated with BMI in men but not in women, in whom protein intake was correlated (P<0.001) with BMI. Linear regression models including dietary components explained up to 10.6 and 21.1 % of BMI variability in men and women, respectively. Sex differences in the association of BMI with total cholesterol, and LDL-cholesterol, may account for the lower risk for CHD in women compared with men of similar BMI reported in the literature for the southern-Europe Mediterranean region. An increases of BMI may be more deleterious in populations in which it is accompanied by other risk factors such as a higher intake of total fat and, particularly, of saturated fatty acids, or lower leisure-time physical activity.

Adult↗
PubMed2002

Heterodimerization of somatostatin and opioid receptors cross-modulates phosphorylation, internalization, and desensitization.

Heterodimerization has been shown to modulate the ligand binding, signaling, and trafficking properties of G protein-coupled receptors. However, to what extent heterodimerization may alter agonist-induced phosphorylation and desensitization of these receptors has not been documented. We have recently shown that heterodimerization of sst(2A) and sst(3) somatostatin receptors results in inactivation of sst(3) receptor function (Pfeiffer, M., Koch, T., Schröder, H., Klutzny, M., Kirscht, S., Kreienkamp, H. J., Höllt, V., and Schulz, S. (2001) J. Biol. Chem. 276, 14027-14036). Here we examine dimerization of the sst(2A) somatostatin receptor and the mu-opioid receptor, members of closely related G protein-coupled receptor families. In coimmunoprecipitation studies using differentially epitope-tagged receptors, we provide direct evidence for heterodimerization of sst(2A) and MOR1 in human embryonic kidney 293 cells. Unlike heteromeric assembly of sst(2A) and sst(3), sst(2A)-MOR1 heterodimerization did not substantially alter the ligand binding or coupling properties of these receptors. However, exposure of the sst(2A)-MOR1 heterodimer to the sst(2A)-selective ligand L-779,976 induced phosphorylation, internalization, and desensitization of sst(2A) as well as MOR1. Similarly, exposure of the sst(2A)-MOR1 heterodimer to the mu-selective ligand [d-Ala(2),Me-Phe(4),Gly(5)-ol]enkephalin induced phosphorylation and desensitization of both MOR1 and sst(2A) but not internalization of sst(2A). Cross-phosphorylation and cross-desensitization of the sst(2A)-MOR1 heterodimer were selective; they were neither observed with the sst(2A)-sst(3) heterodimer nor with the endogenously expressed lysophosphatidic acid receptor. Heterodimerization may thus represent a novel regulatory mechanism that could either restrict or enhance phosphorylation and desensitization of G protein-coupled receptors.

Amides↗