Attenuated 5-HT2 receptor-mediated responses in hindquarters of diabetic rats

James, Gail M.; Hodgson, Wayne Clarence

doi:10.1016/0014-2999(95)00524-2

Cited by 7 publications

(1 citation statement)

References 20 publications

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“…However, it is in agreement with a report that contractile responses of endothelium‐denuded mesenteric arteries from diabetic rats to ET‐1 are unchanged ( Arikawa et al ., 2001 ). Differences in the effects of diabetes on contractile responses to stimulation of GPCR in different arteries have previously been reported ( James & Hodgson, 1995 ). Although the reason for this is not known, these results demonstrate that the upregulation of PKC β 2 and ɛ in mesenteric arteries from diabetic rats is not associated with a generalized increase in the ability of GPCR agonists to activate PKC.…”

Section: Discussionmentioning

confidence: 87%

Role of the PKC/CPI‐17 pathway in enhanced contractile responses of mesenteric arteries from diabetic rats to α‐adrenoceptor stimulation

Mueed

Zhang

MacLeod

2005

British J Pharmacology

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1 Protein kinase C (PKC) may contribute to enhanced contractile responses of arteries from streptozotocin-diabetic rats to stimulation of G-protein coupled receptors. This was investigated by comparing the effects of PKC inhibitors on contractile responses of mesenteric arteries from diabetic and age-matched control rats to noradrenaline (NA) and endothelin-1 (ET-1). The effects of NA and ET-1 on the distribution of three isoforms of PKC implicated in contraction were also determined. In addition, the effect of NA on phosphorylation of CPI-17, a substrate for PKC, was investigated. 2 Contractile responses of endothelium-denuded arteries from diabetic rats to NA were enhanced, but were normalized by PKC inhibition. In contrast, contractile responses to ET-1 were not significantly different, and were blocked to a similar extent by PKC inhibition, in arteries from control and diabetic rats. 3 NA produced only a small increase in particulate levels of PKCe in control arteries (to 12578% of levels in untreated arteries), but a significant increase in particulate PKCa (to 190722%) and a much greater increase in particulate PKCe (to 230719%) in arteries from diabetic rats. ET-1 increased particulate PKCa and e to a similar extent in arteries from control and diabetic rats. 4 NA significantly enhanced CPI-17 phosphorylation from a basal level of 22710 to 7177% of total in arteries from diabetic rats, and this was prevented by PKC inhibition. NA had no detectable effect on CPI-17 phosphorylation in arteries from control rats. 5 These data suggest that NA-induced activation of PKC and CPI-17, its downstream target, is selectively enhanced in arteries from diabetic rats, and mediates the enhanced contractile responses to this agonist.

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Section: Discussionmentioning

confidence: 87%