Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [(3) H]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: England 01.06.2002
• Subjects: Adenylyl Cyclases - metabolism; Animals; Binding Sites - drug effects; Binding, Competitive - drug effects; Cerebral Cortex - chemistry; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Chickens; Cimetidine - analogs & derivatives; Cimetidine - pharmacokinetics; Cyclic AMP - biosynthesis; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Guinea Pigs; Histamine - pharmacology; Histamine Agonists - pharmacology; Histamine Antagonists - pharmacology; Male; Radioligand Assay; Receptors, Histamine H1 - drug effects; Receptors, Histamine H2 - chemistry; Receptors, Histamine H2 - drug effects; Receptors, Histamine H2 - metabolism; Receptors, Histamine H3 - drug effects
• ISSN: 0022-3042

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 [(3) H]tiotidine, a selective H(2) 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 microm) potently and concentration dependently stimulated cAMP production in [(3) H]adenine pre-labelled slices of chick cerebral cortex, displaying an EC(50) value (concentration that produces 50% of maximum response) of 2.65 microm. The effect of HA was mimicked by agonists of HA receptors with the following rank order of potency: HA >or= 4-methylHA (H(2)) >or= N alpha,N alpha-dimethylHA (H(3) >> H(2) = H(1)) >> 2-methylHA (H(1)) >> 2-thiazolylethylamine (H(1)) >or= R alpha-methylHA (H(3)) >> amthamine, dimaprit (H(2)), immepip (H(3), H(4)). The HA-evoked increase in cAMP production in chick cerebral cortex was antagonized by selective H(2) receptor blockers (aminopotentidine >or= tiotidine > ranitidine >> zolantidine), and not significantly affected by mepyramine and thioperamide, selective H(1) and H(3) /H(4) receptor blockers, respectively. A detailed analysis of the antagonistic action of aminopotentidine (vs. HA) revealed a non-competitive mode of action. The binding of [(3) H]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 (K (d)) = 4.42 nm] and high capacity [maximum number of binding sites (B (max) ) = 362 fmol/mg protein]. The relative rank order of HA-ergic drugs to inhibit [(3) H]tiotidine binding to chick cerebrum was: antagonists - tiotidine >> aminopotentidine = ranitidine >or= zolantadine >> thioperamide - triprolidine; agonists - HA >or= 4-methylHA >> 2-methylHA >or=R alpha-methylHA - dimaprit. In conclusion, chick cerebral cortex contains H(2) -like HA receptors that are linked to the cAMP-generating system and are labelled with [(3) H]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 H(2) -like HA receptors or a novel subtype of HA receptors.