H and H2 receptors

Vigorito C, Giordano A. De Caprio L, Vitale DE, Maurea N, Silvestri P, Tuccillo B, Ferrara N, Marone G, Rengo F Effects of histamine on coronary hemodynamics in man role of H, and H2 receptors. J Am Coll Cardiol 1987 10 1207. 

Hf and H Receptors. Histamine exerts its actions by binding to receptors on cell membranes. Two types of histamine receptors, the Hi and H2 receptors, are known specific agonists and antagonists exist for each of these receptors. Black et al. (55) differentiated H and H2 receptors with the compounds, 2-methylhistamine and 4 methylhistamine. 2-Methylhistamine is active on tissues with H receptors 4-methylhistamine is active on tissues with H2 receptors. Classical antihistaminic drugs were developed in the 1930 s these compounds block H but not H2 receptors. Among the clinically used H -blockers are derivatives of ethanolamine, ethylenediamine, alkylamine, piperazine and phenothiazine (32). These agents are valuable in the treatment of... 

Figure 1.9. Comparison of H, and H2 receptor antagonists. Cyclizine shows very little stmctural resemblance of the agonist histamine.

A comprehensive review of histamine receptors in the cardiovascular system has Ijeen published. Histamine lowers blood pressure by causing widespread vasodilatation in most animal species but the effects are complex to analyse. It is clear that both H and H2 receptors are involved, but their distribution and effect varies depending on the species and particular vascular bed under study. Both types of antagonist have to be administered together to fully block many of the vascular effects of... 

TABLE 20.4 H, and H2 Receptor Agonist Activity of Histamine Derivatives ... 

Histamine receptors have been classified into two major subtypes, H, and H2, on the basis of quantitative studies on isolated peripheral tissues. Histamine H,-receptors mediate the contractile actions of histamine on numerous visceral smooth muscles, most notably from the trachea, ileum and uterus of the guinea-pig [36-39]. These responses are antagonized by the classical -antihistamines [36-39] such as mepyramine (1) [36] and diphenhydramine (3) [40] (see Figure 2.1). Histamine also stimulates the secretion of acid by stomach, increases the rate of contraction of guinea-pig isolated atria and inhibits electrically evoked contractions of rat isolated uterine horn [41 ]. However, these responses are not affected by H, -receptor antagonists and have been defined as histamine H2-receptor responses following the development of specific antagonists to these responses such as burimamide [41], cimetidine [42] and ranitidine [43]. The distribution and classification of histamine H,-and H2-receptors in various mammalian peripheral tissues have been reviewed elsewhere [44-46a]. 

Studies with H,- and H2-receptor agonists and antagonists in mammalian brain have indicated that the pharmacological profile of the autoreceptor... 

The H,-agonist, 2-thiazolylethylamine, stimulates cyclic AMP accumulation in guinea-pig hippocampal slices only at relatively high concentrations [165]. The relative potency of 2-thiazolylethylamine in this preparation 7 with respect to histamine (= 100) [165] is intermediate between the values of 26 and 0.3 expected for stimulation of H,- and H2-receptors, respectively, and suggests that much of the response is dependent upon H2-receptor stimulation. However, following maximal stimulation of the H2-component with dimaprit, 2-thiazolylethylamine further elevates cyclic AMP accumulation and the relative... 

Histamine immunoreactive neurons have been identified in the tuberal region of the posterior hypothalamus (tuberomammilary nucleus), projecting to nearly all parts of the brain. Three histamine receptors are known histamine-related functions in the central nervous system (CNS) are regulated at postsynaptic sites by the H and H2 receptors, while the H3 receptor exhibits the features of a presynaptic autoreceptor, mediating the synthesis and release of histamine. The Hi receptor is widely distributed in the CNS. It is present in all areas and layers of the cerebral cortex, limbic system, caudate putamen, nucleus accumbens, thalamus, hypothalamus, mesencephalon, and lower brainstem and spinal cord. The H2 and H3 receptors are also distributed extensively and in a heterogeneous fashion in the CNS. Regarding the role of histamine in the CNS, there is substantial evidence that it plays a role in control of the sleep/wake cycle. Whether the... 

The most commonly occurring adverse effects caused by vancomycin are referred to collectively as red man syndrome. Reactions may range from mild pruritus, erythema, and flushing of the upper body to angioedema and rarely hypotension and cardiovascular collapse. Reactions may be prevented or their severity decreased by extending the infusion time and/or premedication with histamine H, and H2 receptor antagonists. 

Dachman, W. D., Bedarida, G., Blaschke, T. F., and Hoffman, B. B., 1994, Histamine-induced venodilation in human beings involves both H, and H2 receptor subtypes, J. Allergy Clin. Immunol. 93 606-614. 

Garbarg, M., and Schwartz, J. C., 1988, Synergism, between histamine H,- and H2-receptors in the cAMP response in guinea pig brain slices Effects of phorbol esters and calcium. Mol. Pharmacol. 33 38-43. 

---