Inhibition of ornithine decarboxylase does not prevent intestinal smooth muscle hyperplasia in the rat.
The objective of this research is to examine the relationship between intestinal smooth muscle cell proliferation and polyamine metabolism. Proliferation of muscle is induced by serosal application of benzyldimethyltetradecylammonium chloride (BAC) to a segment of rat jejunum. This treatment destroys all of the longitudinal muscle, one-half of the circular muscle, and the myenteric and extrinsic nerves. The remaining muscle cells undergo mitosis and, by 15 days, the number of muscle cells is increased in both the longitudinal and circular muscle layers. Within 12 h after BAC treatment, there is an increase in the activity of ornithine decarboxylase (ODC) that returns to preinjury levels by 4 days. The smooth muscle content of the three polyamines putrescine, spermidine, and spermine is increased 6 h after injury, returning to preinjury levels within 1 day. DL-alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, prevents the transient increases in both ODC activity and the three polyamines in the smooth muscle. In addition to preventing the transient increases in the three polyamines, DMFO has different effects on smooth muscle content of putrescine, spermidine, and spermine. Putrescine content is permanently depleted by DFMO. Spermidine and spermine content is initially decreased within 24 h by DFMO administration. In contrast to the persistent depletion of putrescine by DFMO, spermidine and spermine return to preinjury levels by 2 days. The maximal peak in DNA synthesis occurs 2 days after injury. In DFMO-administered animals, the maximal DNA synthesis occurs 5 days after injury. The increases in smooth muscle wet weight and DNA content 15 days after injury are not affected by DFMO.(ABSTRACT TRUNCATED AT 250 WORDS)
Luck
M S
MS
School of Pharmacy, University of Wisconsin, Madison 53706.
Bass
P
P
D000818:Animals; D015317:Biogenic Polyamines / Q000032:analysis / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D000518:Eflornithine / Q000494:pharmacology; D006965:Hyperplasia; D007422:Intestines / Q000473:pathology*; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology*; D009955:Ornithine Decarboxylase / Q000502:physiology*; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D015317:Biogenic Polyamines; D065108:Ornithine Decarboxylase Inhibitors; D004247:DNA; D009955:Ornithine Decarboxylase; D000518:Eflornithine