dinoprost and enprofylline

Prostaglandins (PGs) F2 alpha and D2 are bronchoconstrictor agents which are released under allergic conditions such as asthma. The efficacy and potency of PGF2 alpha and PGD2 differ in some tissues. We compared the effects of these two PGs in sensitized human parenchymal strips. In six experiments, PGF2 alpha 0.1 and 0.3 microM produced greater contractions than PGD2 at the same concentrations. There were no significant differences between the contractions from the two PGs at concentrations of 0.01, 0.03, 1.0-10 microM and the two PGs appeared to be equipotent. We studied the effects of the anti-asthmatic drug theophylline, and its analogue enprofylline, on the contraction caused by these PGs. Theophylline 100 microM caused no change to the cumulative concentration response curves. However, enprofylline 100 microM reduced the PGF2 alpha-induced contractions.

Topics: Bronchodilator Agents; Dinoprost; Histamine; Humans; Lung; Muscle Contraction; Muscle, Smooth; Prostaglandin D2; Theophylline; Xanthines

The vasomotor effects of theophylline and enprofylline were investigated on circular segments of human coronary artery taken 6 h after death. Isolated arterial segments were examined using a sensitive myograph and isometric contractions were recorded with Grass transducers. The results were compared with those obtained in feline coronary and cerebral arteries. Theophylline and enprofylline induced pronounced relaxation of all types of precontracted arteries. In feline cerebral arteries the potency for eliciting relaxation was slightly higher for theophylline compared with enprofylline, while there was no difference in potency for the methylxanthines in coronary arteries. Prostaglandin F2 alpha frequently induced rhythmic contractions in human, but not in feline coronary arteries. Theophylline increased the amplitude of the rhythmic contractions while this was not seen following administration of enprofylline. Whether this mode of activity by theophylline contributes to its arrhythmogenic properties in-situ requires clarification.

Topics: Animals; Cats; Cerebral Arteries; Coronary Vessels; Dinoprost; Dose-Response Relationship, Drug; Female; Humans; In Vitro Techniques; Middle Aged; Prostaglandins F; Theophylline; Vasoconstriction; Xanthines

In awake, male rats, oral theophylline (TH) or enprofylline (EN; 3-propyl xanthine), 10 to 50 mg/kg b.wt., similarly increased urinary prostaglandin (PG)E2 excretion, by 2- to 3-fold; urinary PGF2 alpha excretion was increased to a lesser extent (50%), while excretion of a PGI2 metabolite, 6-keto-PGF1 alpha, was not altered. In rat renal high-speed supernatant, neither TH nor EN inhibited activity of 15-hydroxyprostaglandin dehydrogenase, an intrarenal PG catabolizing enzyme, suggesting that the increased urinary PG excretion was due to increased synthesis. TH, at all doses that increased urinary PGE2 excretion, also caused dose-related 2-to 4-fold increases in urine volume and urinary excretion of sodium and potassium. In contrast, at low doses EN increased urinary PGE2 excretion without altering urine volume or electrolyte excretion; at the highest dose tested, EN produced a modest diuresis and natriuresis. Pretreatment of rats with indomethacin or meclofenamate (10 mg/kg b.wt., p.o.), chemically dissimilar PG synthesis inhibitors, prevented effects of TH and EN on urinary PG excretion, and also blocked their diuretic and natriuretic effects. Thus, increased renal PGs may be permissive and requisite for the diuretic and natriuretic effects of xanthines, but not sufficient to cause those effects. Enprofylline has been reported (Persson et al., Life Sci. 30: 2181, 1982) to be more active than theophylline as a phosphodiesterase inhibitor, but inactive as an adenosine antagonist, suggesting that the latter action is not required for xanthine stimulation of urinary PG excretion but may be a factor in the diuretic and natriuretic effects.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Consciousness; Dinoprost; Dinoprostone; Diuresis; Hydroxyprostaglandin Dehydrogenases; Indomethacin; Kidney; Male; Meclofenamic Acid; Natriuresis; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Stimulation, Chemical; Theophylline; Xanthines