Converging adrenergic and cholinergic mechanisms in the inhibition of Cl secretion in fish opercular epithelium.
The rate of Cl secretion (Isc) by the opercular epithelium of Fundulus heteroclitus is stimulated by elevations in cyclic AMP (cAMP) levels elicited via beta 1-adrenergic receptor activation, and inhibited by both alpha 2-adrenergic and muscarinic cholinergic receptor activation via mechanisms presently unknown. A comparison of these two inhibitory responses was made using clonidine, an alpha 2-adrenergic agonist, and acetylcholine (ACh), a cholinergic agonist. The dose required for maximum inhibition was 100 times greater for ACh, but in all other respects the responses elicited by both agonists were statistically indistinguishable. Adrenergic antagonists did not diminish the ACh inhibition, and cholinergic antagonists did not diminish the clonidine inhibition, indicating that the two receptor types were distinct from each other. In control tissues and tissues pretreated with agents that increase cAMP levels (isoproterenol, IBMX, forskolin), both ACh and clonidine had no effects on cyclic AMP levels, indicating an inhibitory mechanism independent of adenylate cyclase. Neither Ca-free media nor a variety of calcium antagonists diminished the ACh or clonidine inhibitions. These results suggest that the alpha 2-adrenergic and muscarinic cholinergic pathways converge into a common pathway to inhibit Cl secretion by a mechanism not involving adenylate cyclase or the mobilization of either extracellular or intracellular calcium stores.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002713:Chlorine / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005399:Fishes / Q000378:metabolism*; D007695:Killifishes / Q000378:metabolism*; D008297:Male; D011941:Receptors, Adrenergic / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D014268:Trifluoperazine; D002713:Chlorine; D014700:Verapamil; D000242:Cyclic AMP; D003620:Dantrolene; D003000:Clonidine; D000109:Acetylcholine; D002118:Calcium