Decreased Adenosine 3′: 5′-Monophosphate Response to Isoproterenol in Cystic Fibrosis Leukocytes

Davis, Pamela B.; Braunstein, Marc; Jay, Caroline

doi:10.1203/00006450-197806000-00005

Cited by 33 publications

(23 citation statements)

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“…5. The gland density seen with cholinergic stimulation in our experiments was similar to that previously reported by Kawahata (14) for upper extremities of Japanese males induced to sweat physiologically (mean 183 glands per cm2 for four males aged [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. The number of glands induced to sweat with cholinergic stimulation did not differ between controls and heterozygotes.…”

Section: Controlssupporting

confidence: 77%

Hyposecretion of β-Adrenergically Induced Sweating in Cystic Fibrosis Heterozygotes

Hagiwara

et al. 1987

Pediatr Res

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Section: Controlssupporting

confidence: 77%

Hyposecretion of β-Adrenergically Induced Sweating in Cystic Fibrosis Heterozygotes

Hagiwara

et al. 1987

Pediatr Res

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“…On the cellular level in vitro the measurement of CAMP formation after 0-adrenergic ~t-~ht be as relevant as the measurement of the final cellular response induced by the CAMP in vivo. Hitherto, studies on cAMP responses to isoproterenol stimulation with cultured fibroblasts from CF patients have yielded contradictory results (5,6,10). It is difficult, however, to compare the results of the different studies since many factors can modify the cyclic nucleotide synthesis in cultured cells.…”

mentioning

confidence: 97%

Enhanced Adenosine 3': 5' - Monophosphate Response to Betaadrenergic Stimulation in Cystic Fibrosis Fibroblasts After Removal of Conditioned Medium

et al. 1980

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SUMMARYSkin fibroblasts derived from 6 patients with cystic fibrosis (CF), 1-6 months old, and from 6 age matched donors were investigated for their ability to accumulate cyclic adenosine 3':s'-monophosphate (c-AMP) in response to isoproterenol and prostaglandin E (PGE1) using strictly defined culture conditions. In order to ob&ain, as far as possible,constant protein content and cell number, cultures were synchronized in the early G phase of the cell cycle by growing them in serum free medium bhfore adding stimulating drugs. There were no statistically significant differences both in basal c-AMP or after incubation with theophylline alone. When cultures were thoroughly washed prior to stimulation, c-AMP accumulation in response to isoproterenol was consistently higher (p<0.001) in CF than in normal fibroblasts, whereas response to PGE did not differ significantly. This difference in response can!iot be attributed to differences in doseor time-response curves, or to differential escape of CAMP into the culture medium. Returning the conditioned media (CM) to the cultures after the washing procedure, or omitting the washing procedure altogether, normalized the CAMP response of CF cells. These data indicate that CF fibroblasts "delete" or "add to" the conditioned medium a substance when washed out of the cultures leave the cells hypersensitized to 0-adrenergic stimulation. SPECULATIONThe enhanced cAMP response to isoproterenol stimulation of CFcells is most likely related to the washing off of a soluble substance which is secreted or deleted into the culture medium in excess of normals. This "factor" could exert its effect in the manner of an antagonist regulating catecholamine responsiveness as a part of a negative feed back loop. Water, electrolyte and macromolecular secretions of exocrine cells are controlled by the action of neurotransmitters of the autonomic nervous system (ANs) (11). Since in CF the disturbance of the exocrine secretions is one of the main symptoms, ANS regulated functions have repeatedly been investigated. Clinical observations in CF patients have demonstrated abnormal pupillary reactions (28) and a clearing of the abnormal turbidity of the saliva after guanethidine treatment, which is an antiadrenergic agent (9). Furthermore a paradoxical discordance between the pulmonary response of the CF-patients to isoproterenol and the response to oral theophylline has been shown (30). In rats, chronically treated with isoproterenol or reserpine, morphological and secretory changes of the salivary glands were reported that strongly resembled the ones observed in CF (31,21,22,23). All these observations lend support to the concept that the primary defect in CF could be linked to a derangement of the ANS in the patients. Adrenergic neurotransmitters stimulate their target cells through specific binding to* and 0-receptor sites on the surface of the cells. As a consequence of the binding to O-receptors, cAMP is formed from ATP by the activation of the enzyme adenylate cyclase present in the plasma membran...

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“…The stimulation of intracellular cAMP by isoproterenol has been shown to be reduced in both mononuclear cells and granulocytes from CF patients compared to leukocytes from healthy controls or those with other chronic and acute lung diseases (7). Similarly, in our initial studies, at 3 days postsubculture six CF cell lines had significantly lower net isoproterenol-stimulated cAMP and isoproterenol stimulation ratio compared to six normal cell lines (Table 2).…”

Section: Comparison Of Normal a N D Cf Cell Linesmentioning

confidence: 61%

“…Subsequently, in a larger series of cell lines of lower passage number, this result could not be confirmed (5). Using different culture conditions, we found that the CF fibroblast limes established from normal individuals (8).…”

Section: Speculationmentioning

confidence: 99%

Hormone-stimulated Cyclic AMP Production by Skin Fibroblasts Cultured from Healthy Persons and Patients with Cystic Fibrosis

1980

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Decreased Adenosine 3′: 5′-Monophosphate Response to Isoproterenol in Cystic Fibrosis Leukocytes

Cited by 33 publications

References 0 publications

Hyposecretion of β-Adrenergically Induced Sweating in Cystic Fibrosis Heterozygotes

Hyposecretion of β-Adrenergically Induced Sweating in Cystic Fibrosis Heterozygotes

Enhanced Adenosine 3': 5' - Monophosphate Response to Betaadrenergic Stimulation in Cystic Fibrosis Fibroblasts After Removal of Conditioned Medium

Hormone-stimulated Cyclic AMP Production by Skin Fibroblasts Cultured from Healthy Persons and Patients with Cystic Fibrosis

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