Figure 9.
RvD2 uses PKA to counter-regulate the increase in [Ca2+]i induced by H1 and H3 specific agonists, but uses PKC to counter-regulate the H4 specific agonist. H1 agonist (histamine dimaleate, 10−6 M) (a,b), H3 ((R)-(-)-α-methylhistamine, 10−5 M) (c,d), and H4 agonist (4-methylhistamine dihydrochloride, 10−5 M) (e,f) were added alone (solid red line in a,c,e; first bar in b,d,f). RvD2 (10−8 M) was added followed by an H1 (a,b), H3 (c,d) or H4 (e,f) agonist 30 min later (dotted red line in a,c,e; second bar in b,d,f). PKA inhibitor H89 (10−5 M) was given 30 min prior to addition of H1 (a,b), H3 (b,d) or H4 (e,f) agonist (solid green line in a,c,e; third bar in b,d,f). PKA inhibitor H89 (10−5 M) was given 15 min prior to RvD2 (10−8 M) treatment followed 30 min later by H1 (a,b), H3 (c,d) or H4 (e,f) agonist (dotted green line in a,c,d; fourth bar in b,d,f). PKC inhibitor Ro317549 (10−7 M) was given 30 min prior to addition of H1 (a,b), H3 (c,d) or H4 (e,f) agonist (solid blue line in a,c,e; fifth bar in b,d,f). PKC inhibitor Ro317549 (10−7 M) was given 15 min prior to RvD2 (10−8 M) treatment followed 30 min later by H1 (a,b), H3 (c,d) or H4 (e,f) agonist (dotted blue line in a,c,e; sixth bar in b,d,f). The average [Ca2+]i over time was shown in (a,c,e); change in peak [Ca2+]i was calculated and shown in (b,d,f). Data are mean ± SEM from 4 rats for (a,b), 6 rats for (c–f). * Indicates a significant difference from basal. # Indicates a significant difference from stimulus alone. Arrow indicates addition of histamine receptor subtype agonist.