Abnormalities of prostaglandins and cyclooxygenase enzymes in female patients with slow-transit constipation.

BACKGROUND AND AIMS: Chronic constipation due to slow transit (STC) is more common in female than in male patients. We have previously shown that these gender differences may be due to over expression of progesterone (PG) receptors that alter G protein patterns. We sought to elucidate the mechanisms responsible for the impaired basal colonic motility in female patients with STC. METHODS: Muscle tissues from females with STC and controls with adeno-carcinoma of the colon were studied. Prostaglandins were determined by immunoassay, COX enzymes by Western blot and COX enzymes and progesterone receptors mRNA by RT-PCR. RESULTS: STC patients had impaired colonic motility index, lower TxA(2) and PGF(2) and higher PGE(2) levels than controls. STC had lower COX-1 protein and mRNA levels and higher COX-2 protein and mRNA levels than controls. These abnormalities were reproduced in normal colonic muscle cells treated with PG for 6 h. STC patients had higher PG receptor protein expression and mRNA levels than controls suggesting over expression of these receptors. CONCLUSIONS: These findings suggest that the impaired motility index of STC is due to abnormal levels of prostaglandin and COX enzymes, probably caused by an over expression of PG receptors that make muscle cells more sensitive to circulating levels of PG.