pituitrin and pneumadin

The direct vascular effect of pneumadin (PN) was determined by studying the changes in intracellular free calcium ([Ca2+]i) levels in cultured rat aortic smooth muscle cells maintained between the second and fifth passages. PN evoked a rapid, concentration-dependent, biphasic increase in [Ca2+]i. The [Ca2+]i level rose from a basal value of 108 nM to a maximum increase in peak value of 170 nM. Although the level of maximal [Ca2+]i response evoked by PN was less than with other vasoactive agonists, it was more potent (EC50 0.5 nM) than even endothelin-1 (EC50 3.1 nM). At concentrations > 100 nM, [Ca2+]i elevations induced by PN above basal levels were no longer observed. Pretreatment with dexamethasone (100 nM for 24 hr) resulted in a significant increase (P < 0.01) in the peak [Ca2+]i response (310 nM) to PN. However, the biphasic pattern in the peak [Ca2+]i responses encountered with increasing concentrations of PN remained unaffected. The exaggerated [Ca2+]i response to PN was abolished by preincubation of cells with either the glucocorticoid antagonist mifepristone (RU 486) or the protein synthesis inhibitor cycloheximide. Inclusion of either an AT1 antagonist (losartan), a V1 selective vasopressin antagonist (d(Ch2)5 Tyr (Me) AVP), or an alpha-adrenoceptor antagonist (phentolamine) failed to affect the increases in [Ca2+]i induced by PN. PN-evoked increases in inositol 1,4,5-trisphosphate levels paralleled the [Ca2+]i changes. These data suggest that PN increases Ca2+ mobilization in rat aortic smooth muscle cells via activation of phospholipase C coupled receptors. This effect is up-regulated by dexamethasone.

Topics: Animals; Anti-Inflammatory Agents; Aorta; Calcium; Cells, Cultured; Dexamethasone; Drug Interactions; Inositol 1,4,5-Trisphosphate; Male; Muscle, Smooth, Vascular; Oligopeptides; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Vasopressins

Pneumadin (PNM) is a biologically active decapeptide, originally isolated from mammalian lungs, that has been previously found to acutely stimulate pituitary-adrenocortical axis in rats. The effects of 2-day PNM administration on the atrophic adrenal cortices of rats treated for 8 days with dexamethasone (DX) were investigated. PNM significantly raised adrenal weight and the average volume of adrenocortical cells. The decapeptide strikingly increased ACTH plasma concentration; however, the blood levels of aldosterone and corticosterone, as well as steroid output by adrenal quarters were not apparently affected. In light of these findings the following conclusions can be drawn: (i) PNM enhances the growth of adrenal cortex in DX-administered rats by a mechanism involving the stimulation of ACTH release; and (ii) PNM treatment is probably too short to allow DX-atrophied adrenocortical cells to re-acquire all their differentiated secretory capacities.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Animals; Anti-Inflammatory Agents; Body Weight; Dexamethasone; Female; Neutrophils; Oligopeptides; Organ Size; Paraffin Embedding; Rats; Rats, Wistar; Stimulation, Chemical; Vasopressins

Normal mammalian lungs, including human fetal lungs, contain significant amounts of a decapeptide which releases arginine-vasopressin from the neurophypophysis and therefore has antidiuretic activity. The rat peptide is: Tyr-Gly-Glu-Pro-Lys-Leu-Asp-Ala-Gly-Val-NH2. The peptide from human fetal lungs has Ala instead of Tyr. It may be a normal regulatory substance and its role in the pathogenesis of the syndrome of inappropriate antidiuresis associated with lung diseases merits investigation. In view of its source and action, the antidiuretic lung peptide may be called Pneumadin.

Topics: Amino Acid Sequence; Animals; Diuresis; Dogs; Female; Guinea Pigs; Humans; In Vitro Techniques; Lung; Male; Molecular Sequence Data; Oligopeptides; Rats; Species Specificity; Vasopressins