Cyclic AMP stimulation of Cl- secretion by the opercular epithelium: the apical membrane chloride conductance.
Chloride secretion (Isc) by the opercular epithelium of the teleost, Fundulus heteroclitus, is stimulated by elevations in intracellular cyclic AMP (cAMP) elicited by beta-adrenergic agonists, such as isoproterenol, and is accompanied by a small but significant increase in the transepithelial conductance (Gt). Cupric ions (Cu2+) have been shown to block the apical membrane Cl- channels in this epithelium, leading to a reduction in both the Isc and Gt (Degnan, '85). In the present studies, the effects of Cu2+ on cAMP-elevated and cAMP-depleted epithelia were observed to define the actions of cAMP in this stimulatory process. At a concentration of 5 X 10(-4) M in the mucosal solution, Cu2+ inhibited the Isc 79.8% and reduced the Gt 39.2%. Isoproterenol produced an attenuated stimulation of the Isc in these tissues compared to untreated controls, but had no effect on the Gt. In tissues bathed bilaterally with Cl- -free Ringer, the Isc was virtually abolished and the Gt was reduced 37.0%; neither Cu2+ nor isoproterenol had any effects on the Isc or Gt under this condition. Simultaneous 2 2Na and 3 6 Cl unidirectional flux determinations indicated that the only effects of both isoproterenol and Cu2+ were on the active Cl- secretory flux. An inhibitor of adenylate cyclase, 2',5' dideoxyadenosine (DDA), reduced the Isc and Gt 39.8% and 20.8% respectively. This inhibitor had no additional effects in Cu2+ -treated tissues and the action of Cu2+ on the Gt was reduced in DDA-treated tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
K J
KJ
Degnan
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D004431:Ear, External / Q000502:physiology; D004553:Electric Conductivity; D004848:Epithelium / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D007695:Killifishes; D008297:Male; D012964:Sodium / Q000502:physiology
D002712:Chlorides; D003839:Deoxyadenosines; D007473:Ion Channels; D016048:Dideoxyadenosine; D003300:Copper; C021008:2',5'-dideoxyadenosine; D012964:Sodium; D000242:Cyclic AMP; D007545:Isoproterenol