Increased concentrations of arachidonic acid, prostaglandins E2, D2, and 6-oxo-F1 alpha, and histamine in human skin following UVA irradiation.

The buttock skin of clinically normal human subjects was subjected to approximately 2.5 minimal erythema doses of ultraviolet A irradiation. Deep red erythema developed during irradiation, faded slightly within the next few hours, increased to maximum intensity between 9-15 h, and decreased gradually thereafter although still persisting strongly at 48 h. Suction blister exudates were obtained at 0, 5, 9, 15, 24, and 48 h after irradiation as well as suction blister exudates from a contralateral control site and assayed for arachidonic acid, prostaglandins D2 and E2, and the prostacyclin breakdown product 6-oxo-prostaglandin F1 alpha by gas chromatography-mass spectrometry, and for histamine by radioenzyme assay. Increased concentrations of arachidonic acid and prostaglandins D2, E2, and 6-oxo-prostaglandin F1 alpha were found maximally between 5-9 h after irradiation, preceding the phase of maximal erythema. Elevations of histamine concentration occurred 9-15 h after irradiation, preceding and coinciding with the phase of maximal erythema. At 24 h, still at the height of the erythemal response, all values had returned to near control levels. Hence increased concentrations of arachidonic acid and its products from the cyclooxygenase pathway, and of histamine, accompany the early stages up to 24 h. A causal role in production of the erythema seems likely for these substances although other mediators are almost certainly involved.

Antihypertensive action of bendroflumethiazide: increased prostacyclin production?

A within-patient randomized, double-blind, crossover study was performed to investigate mechanisms of action of bendroflumethiazide in mild essential hypertension. Significant reductions in lying, standing, and postexercise blood pressure were seen after both 3 days and 10 wk treatment with bendroflumethiazide 10 mg daily. Plasma levels of 6-oxo-PGF1 alpha, the chemical hydrolysis product of prostacyclin, were increased by both 3 days and 10 wk therapy with bendroflumethiazide. This raises the possibility that thiazides may reduce peripheral resistance by increasing prostacyclin biosynthesis.

Prostacyclin-dependent activation of adenylate cyclase in a neuronal somatic cell hybrid: prostanoid structure-activity relationships.

1 Prostacyclin activates adenylate cyclase of the NCB-20 neuronal hybrid cell line. 2 There is a guanosine 5'-triphosphate requirement for the activation of adenylate cyclase by 5,6 beta-dihydroprostacyclin (a stable analogue of prostacyclin). 3 Steady-state kinetic analysis of the activation of adenylate cyclase by 5,6 beta-dihydroprostacyclin suggests a simple non-cooperative bimolecular interaction between the ligand and single receptor population. 4 Structure-activity relationships of selected prostanoids elucidated certain functional requirements for activation of adenylate cyclase.

Metabolites of arachidonic acid formed by human gastrointestinal tissues and their actions on the muscle layers.

1. Gas chromatography-mass spectrometry demonstrated the presence of arachidonic acid (AA), 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) in all extracts of homogenized muscle or mucosa from human stomach, terminal ileum or sigmoid colon. Prostaglandin D2 (PGD2), PGE2 or PGF2 alpha were usually found more often in the mucosal extracts. The 12-hydroxy-derivative of AA (12-HETE) was detected in all extracts of the colon but in only some of the other tissues. 2. Most prostanoids tested contracted the longitudinal muscle, the order of potency being U-46619 (an epoxymethano analogue of PGH2) greater than PGE2 greater than PGF2 alpha greater than PGD2; PGI2 usually caused relaxation, whereas its breakdown products or TxB2 had weak and variable effects. 3. U-46619 or, less potently, PGF2 alpha contracted the circular muscle, whereas PGI2 and usually PGE2 caused relaxation. PGD2, 6-keto-PGF1 alpha, 6,15-diketo-PGF1 alpha or TxB2 usually had little or no effect. 4. PGI2 antagonized contractions to some excitatory prostanoids, without greatly affecting contractions to acetylcholine. 5. For both muscle layers there was a gradient in sensitivity to prostanoids along the gastrointestinal tract. The sensitivities were stomach greater than distal ileum greater than sigmoid colon. 6. The results are discussed in relation to gastrointestinal physiology and pathophysiology.

Inflammatory reactions induced by ultraviolet irradiation.

Exposure of human skin to short wavelength ultraviolet (U.V.) leads to increased concentrations of arachidonic acid and prostaglandins E2 and F2, but their role is uncertain. Although the levels of prostaglandins rise as erythema develops the correlation between intensity of erythema and prostaglandin activity is incomplete. There is mounting evidence that prostaglandins may regulate epidermal cell growth and differentiation through a cyclic-AMP dependent mechanism. The possibility therefore arises that prostaglandins, released in response to U. V. exposure, reduce proliferative activity in the exposed epidermis. This can be expected, in turn, to result in protection of skin from the mutagenic action of U. V. irradiation.