Extracellular ATP can activate autonomic signal transduction pathways in cultured equine sweat gland epithelial cells.
Changes in intracellular free calcium concentration ([Ca2+]i) were monitored in a cell line that was derived from the equine sweat gland epithelium. ATP and closely related compounds could increase [Ca2+]i with a rank order of potency of UTP > or = ATP > ADP >> AMP = adenosine = alpha,beta-methylene-ATP. The responses to ATP and to UTP were initiated by the release of calcium from an internal store and subsequently sustained by calcium influx. The rise in [Ca2+]i thus seems to be mediated by P2U receptors that are coupled to phosphoinositidase C. Some desensitisation of this response developed during repeated stimulation with ATP and this was blocked by staurosporine, an inhibitor of protein kinase C, and augmented by a phorbol ester which acts as an exogenous activator of this enzyme. A protein-kinase-C-dependent inhibitory pathway thus seems to become active during repeated stimulation with ATP. ATP and related compounds could also raise cellular cyclic AMP content. The order of potency was ATP > ADP = AMP = adenosine >> UTP, suggesting that this response is mediated via a separate subclass of P2 receptor. The present results demonstrate that ATP can activate autonomic signal-transduction pathways in cultured equine sweat gland cells and suggest that there may be a purinergic component to the control of secretory activity in the equine sweat gland.
Ko
W H
WH
Institute of Physiology, University of Glasgow.
O'Dowd
J J
JJ
Pediani
J D
JD
Bovell
D L
DL
Elder
H Y
HY
Jenkinson
D M
DM
Wilson
S M
SM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006736:Horses / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine; D013545:Sweat Glands / Q000166:cytology / Q000378:metabolism*
D000470:Alkaloids; D010703:Phorbol Esters; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; C021491:glycerophosphoinositol glycerophosphodiesterase; D019311:Staurosporine; D002118:Calcium