Mechanisms underlying postjunctional synergism between responses of the vas deferens to noradrenaline and ATP
Autor: | Neil C.E. Smith, Geoffrey Burnstock |
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Rok vydání: | 2004 |
Předmět: |
Male
medicine.medical_specialty Guinea Pigs Naphthalenes Protein Serine-Threonine Kinases Biology Norepinephrine chemistry.chemical_compound Adenosine Triphosphate Vas Deferens 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Internal medicine Phosphoprotein Phosphatases medicine Prazosin Animals Enzyme Inhibitors Protein Kinase Inhibitors Adrenergic alpha-Antagonists Phorbol 12 13-Dibutyrate Protein Kinase C Protein kinase C Pharmacology rho-Associated Kinases Dose-Response Relationship Drug Intracellular Signaling Peptides and Proteins Vas deferens Drug Synergism Muscle Smooth Adenosine Electric Stimulation Endocrinology Calphostin C medicine.anatomical_structure chemistry Cantharidin Myosin-light-chain phosphatase medicine.symptom Adenosine triphosphate Histamine Muscle Contraction Muscle contraction medicine.drug |
Zdroj: | European Journal of Pharmacology. 498:241-248 |
ISSN: | 0014-2999 |
Popis: | Mechanisms of postjunctional synergism between adenosine 5'-triphosphate (ATP) and noradrenaline were studied in isolated guinea pig vas deferens. Whereas prior exposure to ATP had no significant effect on noradrenaline-mediated contractions, noradrenaline concentration-dependently enhanced ATP-induced contractions. Similarly to noradrenaline, histamine, which also acts via phospholipase-coupled receptors, induced contractions of the vas deferens and enhanced subsequent responses to ATP. Although phorbol-12, 13-dibutyrate (PDBu), a stimulant of protein kinase C (PKC), failed to induce contractions, it significantly potentiated ATP-induced contractions. The PKC inhibitor, Calphostin C, prevented this effect and the noradrenaline-mediated enhancement of ATP-induced contractions. The phosphatase inhibitor cantharidin induced a time- and concentration-dependent tonic contraction and markedly increased subsequent contractions to ATP. It is suggested that noradrenaline potentiates the contractile response of the vas deferens to ATP via a PKC-mediated mechanism. This may involve the inhibition of myosin light chain phosphatase (MLCP) and subsequent calcium sensitisation. |
Databáze: | OpenAIRE |
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