Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Br J Pharmacol. 1995 Mar;114(6):1236-40.

Potentiation by endothelin-1 of 5-hydroxytryptamine responses in aortae from streptozotocin-diabetic rats: a role for thromboxane A2.

Author information

  • 1Department of Pharmacology, Monash University, Clayton, Victoria, Australia.

Abstract

1. We have previously reported maximum responses to 5-hydroxytryptamine (5-HT) are diminished in endothelium-intact and -denuded aortae from rats with streptozotocin-induced diabetes of 2-weeks duration. 2. In the present study, the thromboxane A2/prostaglandin H2 (TP) receptor antagonist GR32191B (1 microM) significantly reduced maximum responses to 5-HT in endothelium-intact aortae from both control and diabetic rats. In the presence of GR32191B, maximum responses to 5-HT, in endothelium-intact aortae from diabetic rats, were still significantly reduced compared to those obtained in aortae from controls. 3. GR32191B (1 microM) had no significant effect on maximum responses to 5-HT in endothelium-denuded aortae from either control or diabetic rats. 4. Interaction between 5-HT (0.1 microM-0.1 mM) and threshold concentrations of endothelin-1 (ET-1) or the thromboxane (Tx)A2-mimetic, U46619, were examined in endothelium-intact and -denuded aortae from control and 2-week streptozotocin-diabetic rats. 5. Maximum responses to 5-HT in the presence of a threshold concentration of ET-1 (3 nM), in endothelium-intact aortae from diabetic rats, were not significantly different from those of control rats. 6. Maximum responses to 5-HT in the combined presence of ET-1 (3 nM) and GR32191B (1 microM), in endothelium-intact aortae from diabetic rats, were significantly reduced compared to those obtained in aortae from controls. 7. Maximum responses to 5-HT in the presence of ET-1 (3 nM) in endothelium-denuded aortae from diabetic rats were significantly reduced compared to those from controls. 8. Maximum responses to 5-HT in the presence of a threshold concentration of U46619 (20 or 30 nM),in endothelium-intact aortae from diabetic rats, were not significantly different from responses of controls.9. Maximum responses to 5-HT in the presence of a threshold (5-20 nM) concentration of U46619, in endothelium-denuded aortae from diabetic rats, were not significantly different from responses of controls.10 The results of the present study indicate that endothelial-derived TxA2 contributes to the contractile response to 5-HT in aortae from control and diabetic rats. Endothelial-derived TxA2 also appears to play a role in the potentiation of 5-HT responses by ET-1 in aortae from diabetic rats.

PMID:
7620714
[PubMed - indexed for MEDLINE]
PMCID:
PMC1510351
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk