Fig. 1.

Rats received an oral administration of linaclotide (3 µg/kg, p.o.) or saline vehicle control daily for 7 days (n = 7–9/group). On day 6, dilute PS (1 mg/ml) was infused into the urinary bladder via transurethral delivery. Another group of sham-treated control rats (n = 5–9) were catheterized but did not receive PS. Bladder and colonic sensitivity was assessed 24 hours after PS in two separate cohorts of animals. Immediately after the final CRD of 60 mm Hg, the spinal cord was isolated for quantification of pERK expression. In another cohort of PS-treated rats (n = 7 to 8/group), the bladder and colon were isolated and permeability was measured in vitro in modified Ussing chambers. LIN, linaclotide; VEH, vehicle.