Role of purinergic receptors in chloride secretion in Caco-2 cells.
Am J Physiol
; 272(6 Pt 1): C1862-70, 1997 Jun.
Article
em En
| MEDLINE
| ID: mdl-9227415
ABSTRACT
Purinergic receptors play an important role in regulating Cl- secretion in epithelial cells. To explore further the role of these receptors in the intestine, we utilized the human intestinal epithelial cell line, Caco-2, grown on permeable membrane supports and assayed for Cl- secretion by measuring the short-circuit current (Isc). Stimulation of Isc by extracellular nucleotides could be detected by day 4 and increased by day 10 postseeding. The magnitude of stimulation of Isc at 10 microM in cells at day 10 was UTP > ATP > UDP > > 2-methylthioadenosine 5'-triphosphate (2-MeS-ATP) = ADP on the apical side and UTP = 2-MeS-ATP = ATP > ADP > > UDP on the basolateral side. Cross-desensitization studies suggested that two different receptors are expressed in the apical membrane, a P2U purinoceptor and a uridine nucleotide receptor. Two different receptors are also expressed in the basolateral membrane, a P2U receptor and another that reacts with both 2-MeS-ATP and ADP. This latter receptor has an unusual pharmacological profile, with a reactivity for 2-MeS-ATP > ADP but not for ATP. Responses to purinergic receptor agonists were inhibited by pretreatment with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, thapsigargin, or quinine. Thus we suggest that an increase in intracellular Ca2+ and subsequent opening of Ca(2+)-activated K+ channel play a role in increasing driving force for Cl- to exit across the apical membrane. The role of the cystic fibrosis transmembrane conductance regulator as a Cl- exit pathway on the apical membrane was also established.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nucleotídeos de Uracila
/
Nucleotídeos de Adenina
/
Trifosfato de Adenosina
/
Cloretos
/
Receptores Purinérgicos
/
Potenciais da Membrana
Limite:
Humans
Idioma:
En
Revista:
Am J Physiol
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos