Corticosteroid modulation of Na(+)-K+ pump-mediated relaxation in maturing airway smooth muscle.
1. The ontogeny of the relaxant influence of the airway electrogenic Na(+)-K+ pump and its potential modulation by corticosteroids were examined in airway smooth muscle (ASM) segments isolated from newborn and adult rabbits. 2. Control and methylprednisolone-treated (MP) ASM segments were half-maximally contracted with methacholine in K(+)-free buffer and the ASM relaxant responses to Na(+)-K+ pump activation were subsequently evaluated. Relative to adult ASM, control newborn ASM showed significantly enhanced maximal relaxation (Rmax) to KCl (62.5 +/- 5.2% vs. 47.8 +/- 5.2%), but no difference in sensitivity (pC2 = -log concentration producing 50% Rmax: 2.18 +/- 0.12 vs. 2.29 +/- 0.09-log M). 3. Exposure of ASM segments to 500 microM methylprednisolone for 1 h potentiated the airway Na(+)-K+ pump activity. A more pronounced effect was obtained in newborn ASM, where both the Rmax and pC2 values were significantly enhanced. In mature ASM, only the Rmax response to KCl was increased in the presence of MP. 4. Collectively, these data demonstrate that: (i) the functional activity of the airway electrogenic Na(+)-K+ pump decreases with post-natal maturation in the rabbit: (ii) corticosteroid treatment potentiates Na(+)-K+ pump activity in rabbit ASM; and (iii) the latter effect of corticosteroids is enhanced in immature airways. 5. The above findings provide new evidence that the airway relaxant response to activation of the electrogenic Na(+)-K+ pump varies ontogenetically and that corticosteroids potentiate the Na(+)-K+ pump activity in an age-dependent manner.
Schramm
C M
CM
Pediatric Pulmonary Division, University of Connecticut School of medicine, Farmington 06030, USA.
Grunstein
M M
MM
D000375:Aging / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008775:Methylprednisolone / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism
D000254:Sodium-Potassium-Exchanging ATPase; D008775:Methylprednisolone