Mechanisms underlying postjunctional synergism between responses of the vas deferens to noradrenaline and ATP

Autor: Neil C.E. Smith, Geoffrey Burnstock
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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