Alteration of contractile properties to serotonin in gastric fundus smooth muscle isolated from streptozotocin (STZ)-induced diabetic rats.
Contractile responses to serotonin (5-HT) of fundic smooth muscle strips isolated from both control and streptozotocin (STZ)-induced diabetic rats were investigated. Contrary to carbachol (CCh) which causes contractile hyperactivity in DM, 5-HT response tended to decrease in DM compared to that of the control. Pindolol (10(-5)M) increased the value of EC50 of the concentration-response to 5-HT about 2.5 times in both the control and DM. After treatment with pindolol, the maximal tension to 5-HT in DM significantly decreased compared to that of the control. Pindolol showed no effect on the contractile response to CCh. Pindolol significantly inhibited the relaxation caused by isoproterenol in DM more than in the control. Mianserin (10(-5) M) increased the EC50 of the response to 5-HT about 2-2.5 times in both groups, but did not cause a significant difference between the control and DM. The Ca(2+)-induced contraction caused hyperreactivity in DM in the presence of 10(-6) M CCh, but that in DM was not significantly different from the control in the presence of 10(-6) M 5-HT. Pretreatment of phorbol 12-myristate 13-acetate (PMA, 10(-5) M) significantly attenuated the response to 5-HT in the control, but not in DM. Results suggest that the contractile response to 5-HT in DM is related to the altered Ca2+ signal transduction system via disturbed protein kinase C (PKC) activity, and that there are alterations of receptor characteristics and of the density in 5-HT receptor subtypes, especially 5-HT1A, during DM development.
2nd Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
B H
BH
Zhu
Y
Y
Sakai
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005748:Gastric Fundus; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D010869:Pindolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011985:Receptors, Serotonin; D008803:Mianserin; D012701:Serotonin; D013311:Streptozocin; D002217:Carbachol; D010869:Pindolol; D011493:Protein Kinase C; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium