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β‐adrenergic activation of Cl secretion and K secretion in guinea pig distal colon acts through distinct signaling pathways
Author(s) -
Halm Susan,
Zhang Jin,
Halm Dan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.998.19
Subject(s) - forskolin , adenylyl cyclase , medicine , protein kinase a , endocrinology , secretion , pertussis toxin , chemistry , phosphodiesterase , rolipram , vasoactive intestinal peptide , g protein , gi alpha subunit , camp dependent pathway , receptor , stimulation , biology , kinase , enzyme , neuropeptide , biochemistry
Cl and K secretion measured as short‐circuit current (Isc) in isolated mucosa from guinea pig distal colon were stimulated by epinephrine (epi). Cl secretory Isc was transient lasting ~5min, while the negative Isc consistent with K secretion persisted indefinitely. 2'5′‐dideoxyadenosine (ddAdo; inhibits adenylyl cyclase, AC) reduced Cl sec whereas rolipram (inhibits phosphodiesterase) caused an increase; neither altered K sec. Peptide‐YY (PYY; acts via receptor inhibiting AC) reduced Cl sec without altering K sec. Pertussis toxin (inhibits G‐protein‐αi) eliminated PYY inhibition. cAMP levels in colonic mucosa increased at 30s after epi followed by a decrease at 10min, but not to control levels. Forskolin [0.1μM] (stimulates AC and K sec) increased cAMP comparable to epi 10min. PYY inhibited the rise in cAMP at 30s epi; ddAdo blunted the rise in cAMP. 8Br‐cAMP [100μM] stimulated K sec, and at 1mM increased Cl sec. Signaling could act via the cAMP‐dependent effectors protein kinase A (PKA) or Epac. H‐89 (inhibits PKA) reduced Cl sec, but not K sec. 8CPT‐2Me‐cAMP (Epac selective analog) partially stimulated K sec at 100μM. Epi did not activate Rap‐1 (Epac sensitive G‐protein). Thus, β‐adrenergic stimulation activated Cl secretion via a cAMP dependent pathway involving PKA, and activated K secretion via a pathway independent of PKA and Rap1 but possibly involving cAMP‐dependent exchange factor Epac. [NIH DK65845]