Heterogeneity of the mechanisms underlying activation of adenylatecyclase by endothelin-1 in rabbit and bovine iris sphincter and tracheal smooth muscles
SPJ-Saudi Pharmaceutical Journal. 1997; 5 (1): 37-45
em Inglês
| IMEMR
| ID: emr-47047
ABSTRACT
In the bovine and rabbit iris sphincters and tracheas, endothelin-l [ET -1] activated adenylate cyclase [AC] in a concentration-dependent manner. The rate of cAMP formation decreased in the order, bovine iris sphincter > rabbit trachea > > rabbit iris sphincter > > bovine trachea. Maximal values for AC activation in bovine iris sphincter and rabbit trachea were 398% and 392% of basal activity respectively. Pretreatment with indomethacin [1 [micro]M], a cyclooxygenase inhibitor, virtually abolished the increase by ET-1 of cAMP levels in rabbit trachea and bovine trachea [96% reduction]. In the rabbit iris sphincter, indomethacin and nordihydroguairetic acid [NDGA] [1 [micro] M] lipoxygenase inhibitor, brought about 60 and 28% reduction of ET -1 response, respectively. Co-treatment with both eicosanoid inhibitors [1 [micro] M, each] eliminated the ET-1-evoked cAMP formation. Quinacrine [50 [micro] M], a phospholipase A2 [PLA2] inhibitor, attenuated cAMP production by ET -1 at a less prominent rate than that of indomethacin [38 to 70% reduction in cAMP increments]. At odds, in the bovine iris sphincter, the cAMP response was unaltered by all prostanoid inhibitors. Moreover, challenge with nicardipine [-a] Ca [2+] channel blocker, trifluoperazine -a calmodulin inhibitor, or staurosporine -a PKC inhibitor, had no significant effect on the responsiveness to ET -1, suggesting lack of mediators in the coupling of ET - receptors to AC system, in the bovine iris sphincter. In conclusion, activation of AC by ET -1 may represent a widespread phenomenon in smooth muscles. The mechanism whereby ET -1 elicits cAMP production is diverse and may include eicosanoids both from cyclooxygenase and lipoxygenase origins as mediators
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Índice:
IMEMR (Mediterrâneo Oriental)
Assunto principal:
Coelhos
/
Traqueia
/
Prostaglandinas
/
Iris
/
Leucotrienos
/
Endotelinas
Limite:
Animais
Idioma:
Inglês
Revista:
Saudi Pharm. J.
Ano de publicação:
1997
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