Histamine H2‐like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [3H]tiotidine binding

• Published in: Journal of neurochemistry Vol. 81; no. 5; pp. 935 - 946
• Main Authors: Zawilska, Jolanta B., Woldan‐Tambor, Agata, Nowak, Jerzy Z.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2002; Blackwell
• Subjects: [3H]tiotidine binding; Biological and medical sciences; Cell receptors; Cell structures and functions; cerebral cortex; chick; cyclic AMP; Fundamental and applied biological sciences. Psychology; histamine receptors; Molecular and cellular biology; Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine); Ligand binding; Cerebral cortex; Central nervous system; Tiotidine; Cyclic AMP; In vitro; Characterization; Histamine; Vertebrata; Chicken; Aves; H2 Histamine receptor; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2002.00870.x

In this study, histamine (HA) receptors in chick cerebral cortex were characterized using two approaches: (1) analysis of the effects of HA‐ergic drugs on the cAMP‐generating system, and (2) radioreceptor binding of [3H]tiotidine, a selective H2 antagonist. HA was a weak activator of adenylyl cyclase in a crude membrane preparation of chick cerebrum. On the other hand, HA (0.1–1000 μm) potently and concentration dependently stimulated cAMP production in [3H]adenine pre‐labelled slices of chick cerebral cortex, displaying an EC50 value (concentration that produces 50% of maximum response) of 2.65 μm. The effect of HA was mimicked by agonists of HA receptors with the following rank order of potency: HA ≥  4‐methylHA (H2) ≥ Nα,Nα‐dimethylHA (H3 ≫ H2 = H1) ≫  2‐methylHA (H1) ≫ 2‐thiazolylethylamine (H1) ≥ Rα‐methylHA (H3) ≫ amthamine, dimaprit (H2), immepip (H3, H4). The HA‐evoked increase in cAMP production in chick cerebral cortex was antagonized by selective H2 receptor blockers (aminopotentidine ≥ tiotidine > ranitidine ≫ zolantidine), and not significantly affected by mepyramine and thioperamide, selective H1 and H3/H4 receptor blockers, respectively. A detailed analysis of the antagonistic action of aminopotentidine (vs. HA) revealed a non‐competitive mode of action. The binding of [3H]tiotidine to chick cortical membranes was rapid, stable and reversible. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of receptor binding site with high affinity [equilibrium dissociation constant (Kd) = 4.42 nm] and high capacity [maximum number of binding sites (Bmax) = 362 fmol/mg protein]. The relative rank order of HA‐ergic drugs to inhibit [3H]tiotidine binding to chick cerebrum was: antagonists – tiotidine ≫ aminopotentidine = ranitidine ≥ zolantadine ≫ thioperamide ≈ triprolidine; agonists – HA ≥ 4‐methylHA ≫ 2‐methylHA ≥Rα‐methylHA ≈ dimaprit. In conclusion, chick cerebral cortex contains H2‐like HA receptors that are linked to the cAMP‐generating system and are labelled with [3H]tiotidine. The pharmacological profile of these receptors is different from that described for their mammalian counterpart. It is suggested that the studied receptors represent either an avian‐specific H2‐like HA receptors or a novel subtype of HA receptors.