In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of AMP to adenosine by ecto-5'-nucleotidase. Although much is known about ecto-5'-nucleotidase, the renal ecto-phosphodiesterase remains uncharacterized. We administered cAMP (10 microM in the perfusate) to 12 different groups of perfused kidneys. AMP was measur...

A Cu-catalyzed new sequence involving the Ullmann type intermolecular C-C followed by an intramolecular C-N coupling and then intramolecular aza-Michael type addition (and oxidation) in a single pot afforded various fused N-heterocyclic acetic acid derivatives as inhibitors of PDE4.

During the perinatal period, lungs undergo changes to adapt to air breathing. The genes involved in these changes are developmentally regulated by various signaling pathways, including the cyclic nucleotide cAMP. As PDE4s are critical enzymes for regulation of cAMP levels, the objective of this study was to investigate PDE4's ontogeny in developing rat lung during the perinatal period. Pulmonar...

Billington, Charlotte K., Sunil K. Joseph, Caroline Swan, Mark G. H. Scott, Timothy M. Jobson, and Ian P. Hall. Modulation of human airway smooth muscle proliferation by type 3 phosphodiesterase inhibition. Am. J. Physiol. 276 (Lung Cell. Mol. Physiol. 20): L412–L419, 1999.— Elevation in cell cAMP content can inhibit mitogenic signaling in cultured human airway smooth muscle (HASM) cells. We st...

This study tested the hypothesis that regulation of 3',5'-cAMP levels in the kidney vasculature is abnormal in spontaneously hypertensive rats. In isolated, perfused kidneys from adult rats (16 weeks of age), isoproterenol similarly increased renal venous 3',5'-cAMP secretion from kidneys of hypertensive versus normotensive Wistar-Kyoto rats. However, a broad-spectrum phosphodiesterase inhibito...

phosphodiesterase-4 inhibitor BAY 19-8004 on lung function and airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). Pulm Pharmacol Ther 2003; 16: 341–347. 5 Hatzelmann A, Morcillo EJ, Lungarella G, et al. The preclinical pharmacology of roflumilast – a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmaco...

A conceptually new three-component reaction was developed to construct a six-membered fused N-heterocyclic ring affording (pyrazolo)pyrimidines/pyridines as potential inhibitors of PDE4. The reaction is catalyzed by triflic acid in acetic acid in the presence of aerial oxygen.