Pharmacomechanical coupling in rat vas deferens: Effects of agents that modulate intracellular release of calcium and protein kinase C activation
| Autor: | N. I. B. Amobi, I. C. H. Smith, D. Sugden |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Intracellular Fluid
Male medicine.medical_specialty medicine.drug_class General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Norepinephrine chemistry.chemical_compound Vas Deferens Internal medicine Phorbol Esters medicine Animals Enzyme Inhibitors General Pharmacology Toxicology and Pharmaceutics Protein Kinase C Protein kinase C Ryanodine Ryanodine receptor Chemistry Vas deferens General Medicine Protein kinase inhibitor Rats Enzyme Activation EGTA Endocrinology medicine.anatomical_structure Calphostin C Phorbol Thapsigargin Calcium Cyclopiazonic acid Muscle Contraction |
| Zdroj: | Life Sciences. 65:145-156 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/s0024-3205(99)00231-3 |
| Popis: | The effects of agents that modulate intracellular release of calcium and protein kinase C (PKC) activation on noradrenaline (NA)-induced contractions of epididymal vas deferens in calcium-free/EGTA (1 mM) medium were investigated. NA (100 microM) or methoxamine (100 microM) evoked repeatable contractions. Clonidine (100-300 microM) was ineffective. The contractions to NA were reduced by procaine (1-10 mM) but not by thapsigargin (0.1-30 microM), ryanodine (1-30 microM) or TMB-8 (1-30 microM). Contractions to cumulative additions of NA (1-100 microM) were enhanced in the presence of cyclopiazonic acid (10 & 30 microM) but not ryanodine (10 & 30 microM). Sequential contractions to NA were not blocked by PKC inhibitors, calphostin C (1 microM) or Ro 31-8220 (1-30 microM) but were reduced by H-7 (1-30 microM), a broad spectrum protein kinase inhibitor. Although RT-PCR experiments detected mRNA for some Ca2+-dependent/DAG-activated and Ca2+-independent/DAG-activated PKC isoforms in epididymal vas deferens, the PKC activators, phorbol 12, 13-dibutyrate (100 microM) or phorbol 12-myristate 13-acetate (100 microM) failed to activate the tissues in calcium-free medium but enhanced subsequent contractions to NA. These results indicate a limited role for intracellular calcium stores and phorbol ester/DAG-sensitive PKC isoforms in NA-induced contraction of epididymal rat vas deferens in calcium-free medium. The results suggest that pharmacomechanical coupling triggered by NA may involve the sensitization of contractile myofilaments to Ca2+ or a Ca2+-independent mechanism. The possible involvement of Ca2+-independent/DAG-insensitive PKC isoforms and agonist-dependent but PKC-independent sensitization pathway is discussed. |
| Databáze: | OpenAIRE |
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