Are so many adrenergic receptor subtypes really present in domestic animal tissues? A pharmacological perspective.

Abstract: Adrenergic receptors (ARs) are the cellular membrane binding sites through which natural catecholamines and sympathomimetic drugs exert their physiological and pharmacological effects. In recent decades, studies to clarify the distribution and function of ARs have been performed mostly on cultured cells, laboratory animals and human target tissues, but little is known about these aspects in domestic animals. This review focuses on AR structure, classification and signalling pathways and on AR subtype distribution in target tissues of some domestic animals, namely dogs, horses and bovines. In these species, different alpha- and beta-AR subtypes have been characterized and the functions controlled by the adrenergic systems have been studied. In the dog, the role played by the adrenergic system in the pathogenesis of cardiovascular disorders and in the modulation of canine aggression has roused particular interest. In dogs affected by dilated cardiomyopathy a significant down-regulation of beta-ARs has been observed both in the heart and circulating lymphocytes. This finding confirms the involvement of the adrenergic system in the pathogenesis and progression of the disorder and suggests new therapeutic strategies. In the horse, AR distribution has been studied in the cardiac, respiratory and gastrointestinal systems as well as in digital veins and arteries. The cardiac beta-ARs in healthy horses seem to be predominantly represented by the beta(1) subtype. In this species, heart failure may increase the expression of the beta(2) subtype, rather than causing AR down-regulation. Different beta- and alpha-AR subtypes have been characterized in the smooth muscle of equine ileum. The sympathetic relaxation of equine ileum smooth muscle seems to depend mainly on beta(3)-AR subtype activation, with minor involvement of the beta(2) subtype. In the respiratory tract, regional differences have been evidenced in the functionality of beta-AR subtype. The beta(2) subtype predominates in all segments but the beta(2) subtype-mediated adenyl cyclase response is tissue-dependent, with higher activity in tracheal membranes than bronchial or pulmonary ones. Both alpha- and beta-AR subtypes are present in the genital tract of cows. Bovine ovarian and myometrial cell membranes express higher concentrations of beta(2)-ARs than the beta(1) subtype, whereas as far as alpha-ARs are concerned, a single class of alpha(1)-ARs and two distinct classes of alpha(2)-AR binding sites have been discriminated. Interestingly, it has been observed that the activation of the sympathetic system could play an important role in the pathogenesis of bovine ovarian cysts as suggested by the modifications in beta-AR levels in the hypophysis and ovary of cows affected by ovarian cysts. In this species, the phenomenon of down-regulation has been well studied in different organs of veal calves treated with clenbuterol as a "partitioning agent". Since differences exist in AR distribution among species, data obtained in laboratory animals or in human beings cannot be extrapolated to domestic animals and further investigation on AR subtypes in domestic animal tissues is necessary.