Bradykinin and phorbol ester but not 5-HT2B receptor activation stimulate phospholipase D activity in the rat stomach fundus.
1. Serotonin has been implicated as a mediator involved in migraine headache, an effect that may involve central 5-HT2B receptor activation. 5-HT2B receptor signal transduction in controversial. 2. Rat stomach fundus contraction to serotonin has been used as a model for 5-HT2B receptor activation. Serotonin-induced contractility involves intracellular calcium release and activation of protein kinase C without stimulation of phosphoinositide (PI) hydrolysis. 3. Since phospholipase D (PLD) activation results in phosphatidic acid production, which can release intracellular calcium and provide diacylglycerol for PKC activation, the purpose of this study was to determine whether the 5-HT2B receptor coupled to PLD activation using the rat stomach fundus as a model system. 4. Using phosphatidylethanol production to measure PLD activity, both bradykinin (0.01-1 microM) and phorbol dibutyrate (PDBu, 1 microM) stimulated PLD activity in rat stomach fundal strips, indicating that this tissue possesses an active PLD system. 5. Under identical conditions, 5-hydroxytryptamine (5-HT) failed to stimulate PLD activity over a concentration range (1 nM-1 microM) documented to induce 5-HT2B receptor-mediated contraction in rat stomach fundus. Thus, the 5-HT2B contractile receptor in rat stomach fundus is not coupled to PLD activation, whereas both bradykinin and phorbol ester do couple to PLD.
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Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
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Cohen
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D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D005748:Gastric Fundus; D020404:Glycerophospholipids / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013270:Stomach / Q000187:drug effects / Q000502:physiology*
D020404:Glycerophospholipids; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; C051521:phosphatidylethanol; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D010739:Phospholipase D; D001920:Bradykinin; D002118:Calcium