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Effects of Phorbol 12,13-diacetate on Human Isolated Bronchus

Effects of Phorbol 12,13-diacetate on Human Isolated Bronchus

B Sarriá, C Pedrós, G Galán, J Cortijo, E J Morcillo

Eur J Pharmacol. 2000 Jun 30;399(1):65-73.

PMID: 10876024

Abstract:

Protein kinase C appears to be involved in the regulation of airway contractility. Phorbol 12,13-diacetate (PDA; 0.01-10 microM), a protein kinase C activator, produced a transient relaxation followed by a sustained contraction of human isolated bronchus. Different protein kinase C inhibitors (calphostin C, staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine) (H-7), nifedipine (NIF; 1 microM) or incubation with Ca(2+)-free medium, inhibited the spasmogenic response to phorbol, while ouabain (10 microM) suppressed only the initial relaxation. These results indicate that the initial relaxation, in response to PDA, is related to the activation of Na(+)/K(+)-ATPase, while the ensuing contraction depends on extracellular Ca(2+) entry.Incubation with PDA (1-5 microM) depressed the maximal relaxation to theophylline and caffeine obtained at 37 degrees C but augmented the spasmogenic responses to methylxanthines (10 mM) obtained in cooled preparations. These effects do not result apparently from increased extracellular entry of Ca(2+), but instead, from facilitation of the release of Ca(2+) from intracellular stores.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP24928152	Phorbol 12,13-diacetate		24928-15-2	Price

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