Nocturnal asthma. Beta 2-adrenoceptors on peripheral mononuclear leukocytes, cAMP- and cortisol-plasma concentrations

To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men an...

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Veröffentlicht in:Chest 1991-11, Vol.100 (5), p.1239-1245
Hauptverfasser: Haen, E, Hauck, R, Emslander, H P, Langenmayer, I, Liebl, B, Schopohl, J, Remien, J, Fruhmann, G
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container_end_page 1245
container_issue 5
container_start_page 1239
container_title Chest
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creator Haen, E
Hauck, R
Emslander, H P
Langenmayer, I
Liebl, B
Schopohl, J
Remien, J
Fruhmann, G
description To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men and ten so far untreated male asthmatic patients at 4-h intervals for 24 h. No difference was seen in the beta 2-adrenoceptor density (Bmax) on pMNL between healthy and asthmatic men (24-h means +/- SE: 908 +/- 59 sites per cell and 821 +/- 54 sites per cell, respectively). The equilibrium dissociation constant (Kd), however, was significantly higher in the asthmatic patients (24-h mean +/- SE: 8.8 +/- 1.2 pmol/L vs 3.0 +/- 0.2 pmol/L in healthy men, p less than 0.0001), which is equivalent to a lower affinity of the beta 2-adrenoceptors for the radioligand 125iodocyanopindolol. Bmax showed a statistically significant circadian variation, but Kd did not. The circadian variation in Bmax was reflected in the basal intracellular cyclic adenosine-monophosphate (cAMP) content of the cells investigated. High Kd values (equivalent to low receptor affinities) tended to be associated with small increases of the intracellular cAMP content after in vitro stimulation by 10(-7) mol/L isoprenaline (isoproterenol) (24-h mean +/- SE: 1.4 +/- 0.2 pmol/10(6) cells; r = -0.529, p = 0.05 at r = -0.549, n = 10). Plasma cAMP concentrations were found to be significantly lower in the asthmatic patients (24-h means +/- SE: 22.9 +/- 1.3 nmol/L vs 29.1 +/- 1.1 nmol/L, p less than 0.0001). Plasma cortisol concentrations were significantly higher in the asthmatic patients (24-h means +/- SE: 0.500 +/- 0.084 mumol/L vs 0.319 +/- 0.063 mumol/L). The results support the hypothesis that a lesion of the beta-adrenergic system contributes to the pathophysiology of atopic bronchial asthma. In the patients investigated in this study, such a lesion could be demonstrated in the affinity rather than in the number of beta 2-adrenoceptors expressed on peripheral cells of the immune system (pMNL). According to present-day knowledge of adrenergic effects on pMNL, such an affinity decrease of beta 2-adrenoceptors could account for overshooting immune responses. In association with other factors influencing respiratory function, it could be responsible for the predominantly nocturnal complaints in atopic bronchial asthma. Plasma cortisol concentrations did not appear to be related to the principal cause of "
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Beta 2-adrenoceptors on peripheral mononuclear leukocytes, cAMP- and cortisol-plasma concentrations</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Haen, E ; Hauck, R ; Emslander, H P ; Langenmayer, I ; Liebl, B ; Schopohl, J ; Remien, J ; Fruhmann, G</creator><creatorcontrib>Haen, E ; Hauck, R ; Emslander, H P ; Langenmayer, I ; Liebl, B ; Schopohl, J ; Remien, J ; Fruhmann, G</creatorcontrib><description>To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men and ten so far untreated male asthmatic patients at 4-h intervals for 24 h. No difference was seen in the beta 2-adrenoceptor density (Bmax) on pMNL between healthy and asthmatic men (24-h means +/- SE: 908 +/- 59 sites per cell and 821 +/- 54 sites per cell, respectively). The equilibrium dissociation constant (Kd), however, was significantly higher in the asthmatic patients (24-h mean +/- SE: 8.8 +/- 1.2 pmol/L vs 3.0 +/- 0.2 pmol/L in healthy men, p less than 0.0001), which is equivalent to a lower affinity of the beta 2-adrenoceptors for the radioligand 125iodocyanopindolol. Bmax showed a statistically significant circadian variation, but Kd did not. The circadian variation in Bmax was reflected in the basal intracellular cyclic adenosine-monophosphate (cAMP) content of the cells investigated. High Kd values (equivalent to low receptor affinities) tended to be associated with small increases of the intracellular cAMP content after in vitro stimulation by 10(-7) mol/L isoprenaline (isoproterenol) (24-h mean +/- SE: 1.4 +/- 0.2 pmol/10(6) cells; r = -0.529, p = 0.05 at r = -0.549, n = 10). Plasma cAMP concentrations were found to be significantly lower in the asthmatic patients (24-h means +/- SE: 22.9 +/- 1.3 nmol/L vs 29.1 +/- 1.1 nmol/L, p less than 0.0001). Plasma cortisol concentrations were significantly higher in the asthmatic patients (24-h means +/- SE: 0.500 +/- 0.084 mumol/L vs 0.319 +/- 0.063 mumol/L). The results support the hypothesis that a lesion of the beta-adrenergic system contributes to the pathophysiology of atopic bronchial asthma. In the patients investigated in this study, such a lesion could be demonstrated in the affinity rather than in the number of beta 2-adrenoceptors expressed on peripheral cells of the immune system (pMNL). According to present-day knowledge of adrenergic effects on pMNL, such an affinity decrease of beta 2-adrenoceptors could account for overshooting immune responses. In association with other factors influencing respiratory function, it could be responsible for the predominantly nocturnal complaints in atopic bronchial asthma. 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Beta 2-adrenoceptors on peripheral mononuclear leukocytes, cAMP- and cortisol-plasma concentrations</title><title>Chest</title><addtitle>Chest</addtitle><description>To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men and ten so far untreated male asthmatic patients at 4-h intervals for 24 h. No difference was seen in the beta 2-adrenoceptor density (Bmax) on pMNL between healthy and asthmatic men (24-h means +/- SE: 908 +/- 59 sites per cell and 821 +/- 54 sites per cell, respectively). The equilibrium dissociation constant (Kd), however, was significantly higher in the asthmatic patients (24-h mean +/- SE: 8.8 +/- 1.2 pmol/L vs 3.0 +/- 0.2 pmol/L in healthy men, p less than 0.0001), which is equivalent to a lower affinity of the beta 2-adrenoceptors for the radioligand 125iodocyanopindolol. Bmax showed a statistically significant circadian variation, but Kd did not. The circadian variation in Bmax was reflected in the basal intracellular cyclic adenosine-monophosphate (cAMP) content of the cells investigated. High Kd values (equivalent to low receptor affinities) tended to be associated with small increases of the intracellular cAMP content after in vitro stimulation by 10(-7) mol/L isoprenaline (isoproterenol) (24-h mean +/- SE: 1.4 +/- 0.2 pmol/10(6) cells; r = -0.529, p = 0.05 at r = -0.549, n = 10). Plasma cAMP concentrations were found to be significantly lower in the asthmatic patients (24-h means +/- SE: 22.9 +/- 1.3 nmol/L vs 29.1 +/- 1.1 nmol/L, p less than 0.0001). Plasma cortisol concentrations were significantly higher in the asthmatic patients (24-h means +/- SE: 0.500 +/- 0.084 mumol/L vs 0.319 +/- 0.063 mumol/L). The results support the hypothesis that a lesion of the beta-adrenergic system contributes to the pathophysiology of atopic bronchial asthma. In the patients investigated in this study, such a lesion could be demonstrated in the affinity rather than in the number of beta 2-adrenoceptors expressed on peripheral cells of the immune system (pMNL). According to present-day knowledge of adrenergic effects on pMNL, such an affinity decrease of beta 2-adrenoceptors could account for overshooting immune responses. In association with other factors influencing respiratory function, it could be responsible for the predominantly nocturnal complaints in atopic bronchial asthma. Plasma cortisol concentrations did not appear to be related to the principal cause of "nocturnal asthma;" they rather reflected an endogenous defense mechanism to the disease.</description><subject>Adult</subject><subject>Asthma - metabolism</subject><subject>Circadian Rhythm - physiology</subject><subject>Cyclic AMP - blood</subject><subject>Humans</subject><subject>Hydrocortisone - blood</subject><subject>Leukocytes, Mononuclear - chemistry</subject><subject>Male</subject><subject>Receptors, Adrenergic, beta - analysis</subject><subject>Reference Values</subject><subject>Respiratory Function Tests</subject><issn>0012-3692</issn><issn>1931-3543</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNotkc1P3DAUxK0KtF0o914q-cSpCXYc2_gIKwqV6IdU7tHDeWkCjh1sR9X-9zWwp6fR_PSkmSHkM2c1F_rywo6Ycs0Zq2XNG2E-kC03gldCtuKIbBnjTSWUaT6Sk5SeWNHcqA3ZcCW1FGpL1p_B5jV6cBRSHmeo6TVmoE0FfUQfLC45xESDpwvGaRkxFnQOPvjVOoRIHa7Pwe4zpq_UXv34XVHwPbUh5ikFVy0O0gxFe4s-R8hT8OkTOR7AJTw73FPy59vNw-6uuv91-313dV-NplUVKBiMQSEUNAi2l4NmRgpELVE9ikFozoahaWRJDFr3wFG3yLBlivdSi1Ny_v51ieFlLUV185QsOgcew5o63bRtwUwBvxzA9XHGvlviNEPcd4eWis_e_XH6O_6bInYlknOFFt3bAk_hrcKyQye71x3Ef0c_fUY</recordid><startdate>19911101</startdate><enddate>19911101</enddate><creator>Haen, E</creator><creator>Hauck, R</creator><creator>Emslander, H P</creator><creator>Langenmayer, I</creator><creator>Liebl, B</creator><creator>Schopohl, J</creator><creator>Remien, J</creator><creator>Fruhmann, G</creator><general>American College of Chest Physicians</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19911101</creationdate><title>Nocturnal asthma. Beta 2-adrenoceptors on peripheral mononuclear leukocytes, cAMP- and cortisol-plasma concentrations</title><author>Haen, E ; Hauck, R ; Emslander, H P ; Langenmayer, I ; Liebl, B ; Schopohl, J ; Remien, J ; Fruhmann, G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h946-a6af99e336a2eacd5f70953ee75e6b3f3710ff225931a77da1e74e0e4061d573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Adult</topic><topic>Asthma - metabolism</topic><topic>Circadian Rhythm - physiology</topic><topic>Cyclic AMP - blood</topic><topic>Humans</topic><topic>Hydrocortisone - blood</topic><topic>Leukocytes, Mononuclear - chemistry</topic><topic>Male</topic><topic>Receptors, Adrenergic, beta - analysis</topic><topic>Reference Values</topic><topic>Respiratory Function Tests</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Haen, E</creatorcontrib><creatorcontrib>Hauck, R</creatorcontrib><creatorcontrib>Emslander, H P</creatorcontrib><creatorcontrib>Langenmayer, I</creatorcontrib><creatorcontrib>Liebl, B</creatorcontrib><creatorcontrib>Schopohl, J</creatorcontrib><creatorcontrib>Remien, J</creatorcontrib><creatorcontrib>Fruhmann, G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Chest</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haen, E</au><au>Hauck, R</au><au>Emslander, H P</au><au>Langenmayer, I</au><au>Liebl, B</au><au>Schopohl, J</au><au>Remien, J</au><au>Fruhmann, G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nocturnal asthma. Beta 2-adrenoceptors on peripheral mononuclear leukocytes, cAMP- and cortisol-plasma concentrations</atitle><jtitle>Chest</jtitle><addtitle>Chest</addtitle><date>1991-11-01</date><risdate>1991</risdate><volume>100</volume><issue>5</issue><spage>1239</spage><epage>1245</epage><pages>1239-1245</pages><issn>0012-3692</issn><eissn>1931-3543</eissn><abstract>To evaluate pathophysiologic mechanisms of the predominantly nocturnal complaints in atopic bronchial asthma, the expression and function of beta 2-adrenoceptors on peripheral mononuclear leukocytes (pMNL), the cAMP--as well as the cortisol--plasma concentrations were studied in eight healthy men and ten so far untreated male asthmatic patients at 4-h intervals for 24 h. No difference was seen in the beta 2-adrenoceptor density (Bmax) on pMNL between healthy and asthmatic men (24-h means +/- SE: 908 +/- 59 sites per cell and 821 +/- 54 sites per cell, respectively). The equilibrium dissociation constant (Kd), however, was significantly higher in the asthmatic patients (24-h mean +/- SE: 8.8 +/- 1.2 pmol/L vs 3.0 +/- 0.2 pmol/L in healthy men, p less than 0.0001), which is equivalent to a lower affinity of the beta 2-adrenoceptors for the radioligand 125iodocyanopindolol. Bmax showed a statistically significant circadian variation, but Kd did not. The circadian variation in Bmax was reflected in the basal intracellular cyclic adenosine-monophosphate (cAMP) content of the cells investigated. High Kd values (equivalent to low receptor affinities) tended to be associated with small increases of the intracellular cAMP content after in vitro stimulation by 10(-7) mol/L isoprenaline (isoproterenol) (24-h mean +/- SE: 1.4 +/- 0.2 pmol/10(6) cells; r = -0.529, p = 0.05 at r = -0.549, n = 10). Plasma cAMP concentrations were found to be significantly lower in the asthmatic patients (24-h means +/- SE: 22.9 +/- 1.3 nmol/L vs 29.1 +/- 1.1 nmol/L, p less than 0.0001). Plasma cortisol concentrations were significantly higher in the asthmatic patients (24-h means +/- SE: 0.500 +/- 0.084 mumol/L vs 0.319 +/- 0.063 mumol/L). The results support the hypothesis that a lesion of the beta-adrenergic system contributes to the pathophysiology of atopic bronchial asthma. In the patients investigated in this study, such a lesion could be demonstrated in the affinity rather than in the number of beta 2-adrenoceptors expressed on peripheral cells of the immune system (pMNL). According to present-day knowledge of adrenergic effects on pMNL, such an affinity decrease of beta 2-adrenoceptors could account for overshooting immune responses. In association with other factors influencing respiratory function, it could be responsible for the predominantly nocturnal complaints in atopic bronchial asthma. Plasma cortisol concentrations did not appear to be related to the principal cause of "nocturnal asthma;" they rather reflected an endogenous defense mechanism to the disease.</abstract><cop>United States</cop><pub>American College of Chest Physicians</pub><pmid>1657536</pmid><doi>10.1378/chest.100.5.1239</doi><tpages>7</tpages></addata></record>
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ispartof Chest, 1991-11, Vol.100 (5), p.1239-1245
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subjects Adult
Asthma - metabolism
Circadian Rhythm - physiology
Cyclic AMP - blood
Humans
Hydrocortisone - blood
Leukocytes, Mononuclear - chemistry
Male
Receptors, Adrenergic, beta - analysis
Reference Values
Respiratory Function Tests
title Nocturnal asthma. Beta 2-adrenoceptors on peripheral mononuclear leukocytes, cAMP- and cortisol-plasma concentrations
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