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β‐adrenergic activation of Cl secretion and K secretion in guinea pig distal colonic mucosa proceeds via separate receptor complexes
Author(s) -
Halm Susan,
Zhang Jin,
Halm Dan
Publication year - 2010
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.24.1_supplement.610.17
Subject(s) - adenylyl cyclase , medicine , endocrinology , chemistry , guinea pig , receptor , secretion , bicarbonate , forskolin , biology
Epinephrine (epi) stimulated ion secretion in isolated mucosa from guinea pig distal colon, measured as short‐circuit current. Epi responses included transient Cl (0~5 min) and sustained K secretion (sec). ICI‐118551 (β2‐selective antagonist) inhibited Cl sec (Kd = 2.7 nM), even though inhibition of K sec required combined β1/β2 antagonism. Co‐immunoprecipitation of β1 and β2 adrenergic receptors (βAdrR) provided support for this combined action. Both β1AdrR and β2AdrR also co‐IPed with arrestin‐2, suggesting an alternate signaling path. Whereas dideoxyadenosine (ddAdo; inhibits transmembrane adenylyl cyclase, tmAC) inhibited only Cl sec, KH7 (inhibits soluble adenylyl cyclase, sAC) inhibited only K sec. Consistent with bicarbonate dependence for sAC, sustained K sec was 42% smaller in HEPES buffered bathing media (CO2/HCO3 free), without altering transient Cl sec. Immunoblot for sAC indicated a presence of 54 and 74 kDa bands, consistent with sAC isoforms found in other tissues. ddAdo suppressed the biphasic epi activation of cAMP levels; KH7 left the early transient cAMP unaltered but lowered sustained levels; early cAMP transients remained in the absence of bicarbonate with sustained levels lowered. Thus, β2AdrR activation produced Cl sec via a transient cAMP elevation from tmAC, while β1AdrR/β2AdrR activation produced K sec via a sustained cAMP from sAC that was bicarbonate dependent. [NIH DK65845]