A role for protein kinase C in the attenuated response to 5-hydroxytryptamine in aortas from streptozotocin-diabetic rats.
We investigated protein kinase C participation in the contractile response to 5-hydroxytryptamine (5-HT), and in the interaction between 5-HT and endothelin-1, in aortas from control and diabetic rats. Diabetic rats display attenuated reactivity to 5-HT (i.e., approximately 47% of control maximum). The protein kinase C inhibitor calphostin C (1 microM) significantly reduced responses to 5-HT only in aortas from control rats. In diabetic rats, maximum responses to 5-HT, in the presence of endothelin-1 (3 nM), were not significantly different to controls. The additional presence of calphostin C significantly reduced responses only in aortas from diabetic rats. These results may indicate an abnormality in the protein kinase C second messenger system during diabetes.
James
G M
GM
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Hodgson
W C
WC
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D019332:Endothelin-1 / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*
D001786:Blood Glucose; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D012701:Serotonin; D011493:Protein Kinase C; C058819:calphostin C