Byssinosis: role of polymer length on the effect of tannin on the airway beta-adrenergic receptor.
Tannin, isolated from cotton bracts and implicated in the pathogenesis of byssinosis, inhibits isoproterenol and forskolin-stimulated cAMP release from airway cells in part by decreasing cell surface beta-adrenergic receptor number and uncoupling the beta-adrenergic receptor from its stimulatory G-protein (Gs) and in part by inhibiting adenylyl cyclase activity. We have hypothesized that cotton tannin, because of its long polymer length, interacts with the hydrophobic binding pocket of the beta-adrenergic receptor and alters beta-adrenergic receptor binding and Gs coupling. In these studies, tannins of three different polymer lengths and molecular masses were isolated from cotton bracts using sequential Amicon ultrafiltration [molecular mass > 10, 000 (YM10 retentate), 1,000-10,000 (YM10 filtrate), and 1,000-5,000 Da (YM2 retentate)]. The YM10 retentate (25 microg/ml) decreased chloride secretion (Jnet = 1.11 +/- 0.28 (control) to 0.59 +/- 0.18 microEq/cm2.h, p < 0.05, n = 6), decreased cell surface beta-adrenergic receptor number (18.0 +/- 1.8 (control) to 10.6 +/- 0.9 fmol/mg protein, p < 0.02, n = 4), and inhibited forskolin-stimulated cAMP release (5,254 +/- 1,290 (control) to 2, 968 +/- 620 pmol/mg protein, p < 0.01, n = 8). In contrast, neither the YM10 filtrate nor the YM2 retentate had any effect on net chloride secretion, beta-adrenergic cell surface receptor number, or forskolin-stimulated cAMP release. We conclude that polymer length is essential for the effect of tannin on the beta-adrenergic receptor and on adenylyl cyclase.
University of Connecticut Health Center, Farmington, CT 06030, USA.
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D000818:Animals; D001704:Biopolymers / Q000502:physiology*; D002095:Byssinosis / Q000209:etiology*; D002417:Cattle; D002712:Chlorides / Q000032:analysis / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D003368:Gossypium / Q000737:chemistry; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D008970:Molecular Weight; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000187:drug effects*
D001704:Biopolymers; D002712:Chlorides; D047348:Hydrolyzable Tannins; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000242:Cyclic AMP