Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of alpha 1A -adrenoceptors in the regulation of opioid secretion from the adrenal glands of streptozotocin-induced diabetic rats (STZ-diabetic rats) was examined in an attempt to determine the mechanism of plasma glucose-lowering action of caffeic acid. In agreement with a previous report, we showed that caffeic acid produced a dose-dependent lowering of the plasma glucose concentration in STZ-diabetic rats along with an increase of plasma beta-endorphin-like immunoreactivity (BER). These actions of caffeic acid were abolished by pretreatment with WB 4101 or RS 17 056 at doses sufficient to block alpha 1A -adrenoceptors. In addition, naloxone and naloxonazine at doses effective for blocking opioid micro -receptors abolished the plasma glucose-lowering action of caffeic acid. Also, unlike that in wild-type diabetic mice, caffeic acid failed to produce a plasma glucose lowering effect in opioid micro -receptor knockout diabetic mice. We observed that caffeic acid could enhance BER release from isolated rat adrenal medulla in a concentration-dependent manner; inhibitors of alpha 1A -adrenoceptors such as WB 4101 and RS 1705 abolished this action. Investigations of the signal pathways further supported that activation of alpha 1A -adrenoceptor is responsible for the stimulatory effect of caffeic acid on BER secretion from the adrenal medulla. In the presence of U73312, a specific inhibitor of phospholipase C, the caffeic acid-induced increase of BER was reduced in a concentration-dependent manner, but it was not affected by U73343, the negative control of U73312. Chelerythrine and GF 109203X also diminished the action of caffeic acid at concentrations sufficient for inhibiting protein kinase C. Moreover, bilateral adrenalectomy in STZ-diabetic rats resulted in the loss of this plasma glucose-lowering effect of caffeic acid, and there was no increase in plasma BER with caffeic acid. Therefore, beta-endorphin release from the adrenal gland appears to be responsible for the lowering of plasma glucose in STZ-diabetic rats induced by caffeic acid, through the activation of alpha 1A -adrenoceptors.
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PMID:Release of beta-endorphin by caffeic acid to lower plasma glucose in streptozotocin-induced diabetic rats. 1277 69

1. Mechanisms involved in Ca(2+) sensitization of contractile elements induced by the activation of muscarinic receptors in membrane-permeabilized preparations of the rat proximal and distal colon were studied. 2. In alpha-toxin-permeabilized preparations from the rat proximal and distal colon, Ca(2+) induced a rapid phasic and subsequent tonic component. After Ca(2+)-induced contraction reached a plateau, guanosine 5'-triphosphate (GTP) and carbachol (CCh) in the presence of GTP further contracted preparations of both the proximal and distal colon (Ca(2+) sensitization). Y-27632, a rho-kinase inhibitor, inhibited GTP plus CCh-induced Ca(2+) sensitization more significantly in the proximal colon than in the distal colon. 3. Y-27632 at 10 microm had no effect on Ca(2+)-induced contraction or slightly inhibited phorbol-12,13-dibutyrate-induced Ca(2+) sensitization in either proximal or distal colon. Chelerythrine, a protein kinase C inhibitor, inhibited GTP plus CCh-induced Ca(2+) sensitization in the distal colon, but not in the proximal colon. The component of Ca(2+) sensitization that persisted after the chelerythrine treatment was completely inhibited by Y-27632. 4. In beta-escin-permeabilized preparations of the proximal colon, C3 exoenzyme completely inhibited GTP plus CCh-induced Ca(2+) sensitization, but PKC(19-31) did not. In the distal colon, C3 exoenzyme abolished GTP-induced Ca(2+) sensitization. It inhibited CCh-induced sensitization by 50 % and the remaining component was inhibited by PKC(19-31). 5. These results suggest that both protein kinase C and rho pathways in parallel mediate the Ca(2+) sensitization coupled to activation of muscarinic receptors in the rat distal colon, whereas the rho pathway alone mediates this action in the proximal colon.
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PMID:Mechanisms involved in carbachol-induced Ca(2+) sensitization of contractile elements in rat proximal and distal colon. 1515 78

We previously demonstrated that Ca(2+) sensitization has an essential role for carbachol-induced contraction in the longitudinal muscle of the rat distal colon. In the present study, we extended these studies to clarify the role of Ca(2+) sensitization in contraction induced by the activation of muscarinic receptors in the circular muscle of the rat distal colon. Carbachol induced a rapid phasic contraction followed by a sustained contraction that was significantly lower than the phasic and was superimposed with the rhythmic contractions. The extent of increase in intracellular Ca(2+) concentration that was measured simultaneously with tension recording was dissociated from the phasic contraction, whereas it exhibited to a similar extent as sustained contraction. In alpha-toxin-permeabilized preparations, Ca(2+) induced contraction comprising a rapid phasic and a subsequent low sustained component. After Ca(2+)-induced sustained contraction reached a constant level, guanosine triphosphate (GTP) addition resulted in the enhancement of contractile force in a concentration-dependent manner. Carbachol in the presence of GTP caused a further minimal increase in tension (Ca(2+) sensitization). Chelerythrine, a protein kinase C (PKC) inhibitor, inhibited carbachol-induced Ca(2+) sensitization but not GTP-induced Ca(2+) sensitization. In contrast, Y-27632, a Rho kinase inhibitor, inhibited GTP-induced Ca(2+) sensitization but not that induced by carbachol. Phorbol 12,13-dibutyrate, a PKC activator, increased the sustained contraction. These results suggest that the activation of muscarinic receptor with carbachol induces Ca(2+) sensitization via activation of PKC, but this action is minor in the circular muscle of the rat distal colon as a result of limited coupling between muscarinic receptors and Ca(2+) sensitization via the PKC pathway.
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PMID:A minor role for Ca2+ sensitization in sustained contraction through activation of muscarinic receptor in circular muscle of rat distal colon. 1731 45