title: Mechanisms of the enhanced contractile response to a low concentration of phorbol 12,13-dibutyrate in thoracic aorta isolated from rats with dietary magnesium deficiency.
abstract: The mechanisms underlying the enhanced contractile response to phorbol 12,13-dibutyrate (PDBu) were examined in de-endothelialized thoracic aortas isolated from rats with dietary magnesium (Mg) deficiency. PDBu (1.0 nM)-induced contractions were significantly larger in Mg-deficient rats than in the controls. The contraction was completely inhibited by nifedipine, removal of external Ca2+ or by l-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7). PDBu (1.0 nM) and phorbol 12-myristate 13-acetate (1.0 microM) significantly decreased the KD value and increased the Bmax for the binding of [3H]PN200-110 to the aortas. The degree of the decrease in the KD value was significantly greater in Mg-deficient rats than in the controls. The PDBu-induced decrease in the KD value was abolished by H7. These results suggest that activation of protein kinase C by phorbol esters may participate in the activation of L-type Ca2+ channels, which increases both the affinity of [3H]PN200-110 binding and the magnitude of the external Ca(2+)-dependent contraction. Dietary Mg-deficiency may enhance these processes.
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, Kagoshima University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: N
authors.initials: N
authors.lastname: Anai
authors.forename: A
authors.initials: A
authors.lastname: Miyamoto
authors.forename: S
authors.initials: S
authors.lastname: Ishiguro
authors.forename: A
authors.initials: A
authors.lastname: Nishio
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001665:Binding Sites; D002118:Calcium; D015220:Calcium Channels; D004032:Diet; D008274:Magnesium; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015220:Calcium Channels; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D008274:Magnesium; D009543:Nifedipine; D002118:Calcium