Representative images of rat mesenteric arterioles and venules 5 seconds after injection of 200 nM kg^-1 FITC-N/OFQ into the mesenteric artery with (C,D) and without (A,B) N/OFQ (added 15 sec prior to FITC-N/OFQ and labelled T₁₅) competing for the same NOP receptor site.

<p>The areas highlighted by arrows indicate binding of FITC-N/OFQ to NOP (FITC-N/OFQ-NOP) and thus sparse distribution of NOP receptors on the endothelium in this animal.</p

The effect of UFP-101 on cardiovascular variables: mean arterial pressure (MAP, mmHg; upper panel) and heart rate (beats per minute, bpm; lower panel) were measured in anesthetised rats at baseline (T₀), this being 24 hours after i.v. injection with 1 mg kg^-1 + 0.5 mg kg^-1 (LPS, n=6; LPS + UFP-101, n=6) or saline (control, n=6; UFP-101, n=6).

<p>Measurements were repeated 40 minutes after baseline (T₄₀) in response to i.v. injection of 150 nM kg^-1 UFP-101 (LPS + UFP-101, UFP-101 groups) or saline (control; LPS, groups). Values are median, with open bars representing the 50^th-75^th percentile, grey bars the 25^th-50^th percentile and upper and lower error bars representing the maximum and minimum respectively.</p

Characterisation of FITC-N/OFQ (F-N/OFQ) at recombinant NOP and classical opioid receptors on CHO cells.

<p><b>A</b>: Binding affinity of F-N/OFQ and a range of opioid receptor subtype selective reference compounds. F-N/OFQ shows high selectivity for NOP over classical opioid receptors (mean (range) of up to 4 experiments.) *curves did not saturate K_i estimated between 1 and 10µM. <b>B</b>: Both N/OFQ and F-N/OFQ behave as full agonists on recombinant human NOP. These data are stimulation factor = agonist stimulated specific binding / basal specific binding (mean <u>+</u>SEM, <i>n</i>=8).</p

The effect of UFP-101 on macromolecular leak and leukocyte rolling <i>in vivo</i>: macromolecular leak (percentage change in interstitial FITC-BSA fluorescence from baseline, upper panel) and leukocyte rolling (per minute, baseline and after treatment, lower panel) in post capillary venules (<40 µm) within the anesthetised rat mesentery preparation.

<p>Measurements were taken in response to i.v. injection of 150 nM kg^-1 UFP-101 (LPS + UFP-101 and UFP-101 groups) or saline (control and LPS groups). Values are median, with open bars representing the 50^th-75^th percentile, grey bars the 25^th-50^th percentile and upper and lower error bars representing the maximum and minimum respectively. ^*increased compared to control.</p