Evidence for α-adrenergic receptors acting through the guanylate cyclase system in human cultured thyroid cells

Abstract

In order to investigate the presence of \ g = a \ \ x = r e q -\ adrenergic receptors in human thyroid, we have studied the effect of \g=a\-adrenergicagonists and antagonists on cGMP cellular content of human thyroid cells in primary culture. Epinephrine as well as TSH were not able to modify the cGMP cellular levels, while norepinephrine significantly increased cGMP accumulation already at 10 nM, a dose inactive on cAMP accumulation. A non selective \g=a\-adrenergicantagonist, phentolamine, significantly inhibited cGMP accumulation induced by norepinephrine. Norepinephrine-induced cGMP accumulation was unaffected by prazosin, an \g=a\1-adrenergic antagonist, but was abolished by yohimbine, an \g=a\2-adrenergic antagonist. Phenylephrine, an \g=a\-adrenergicagonist, produced an increase of cellular cGMP levels without modifying cAMP content. In the presence of TSH, the cGMP response to norepinephrine was not modified; however, the increase of cAMP levels was inhibited by norepinephrine at doses inactive on cAMP accumulation, but active on cGMP levels. The present results demonstrate the existence in human thyroid cells of \g=a\2-adrenergic receptors, regulating the guanylate cyclase system. It may be postulated that the counter-regulation exerted by \g=a\-adrenergicagonists on the response to TSH operates on the TSH-dependent adenylate cyclase. Sympathetic nerves have been found to supply the follicle cells in the thyroid of man and several mammals, and sympathetic activation has been shown to enhance thyroid hormone secretion via adrenergic receptors (Melander 1978). Subsequently, existence of ß-adrenergic receptors, acting through the adenylate cyclase system, has been demonstrated in human cultured thyroid cells ). In addition a potentiating effect of a-adrenergic antagonists on TSH action, together with the results of simultaneous stimula¬ tion with norepinephrine and TSH, suggest the presence of a-adrenergic receptors involved in the counter-regulation of TSH action ).In order to confirm the existence of -receptors in thyroid cells and to characterize their action in modulating the response to TSH, we have studied cyclic AMP and GMP levels in human thyroid cultured cells in response to an acute challenge with catecholamines or to an a-adrenergic agonist such as phenylephrine, in the presence and absence of TSH and of -or a2-adrenergic antagonists.The results indicate that an a2-adrenergic receptor modulates the TSH action through a guanylate cyclase system. Materials and Methods

Effects of α-adrenoceptor agonists and antagonists on thyroid hormone secretion

“…Moreover, -adrenoceptor acti¬ vation in human thyroid slices has been shown to enhance cyclic GMP accumulation , and this is of interest since, at least in the dog thyroid, cyclic GMP accumulation is known to enhance the cyclic AMP degradation (Dumont et al 1984). Regard¬ ing the suggested subdivision of the a-adrenoceptors, studies with various more or less selective and a2-adrenoceptor agonists and antagonists have suggested that in the mouse thyroid, the inhibitory -adrenoceptor is of ai-subtype (Muraki et al 1982) whereas in dog and human thyroid it is more of an a2-subtype (Yamashita et al 1980;Brandi et al 1983). Whether -adreno¬ ceptor activation modulates thyroxine secretion from human or dog thyroid is not known.…”

Effect of trilinolein on cyclic nucleotide formation in human platelets: relationship with its antiplatelet effect and nitric oxide synthesis

“…Although some early studies claimed that cyclic GMP was transiently increaesd 10 s after platelets had been mixed with adrenaline (Jakobs et al, 1974), we could not confirm such a stimulatory effect of adrenaline on cyclic GMP. In other tissues, cyclic GMP was found to be increased by adrenaline in gastric mucosa (Ruoff, 1977) amd glioma cells (Schwartz, 1976), while it was not changed in thyroid cells (Brandi et al, 1983), enterocytes (Guandalini et al, 1982) or adrenal cells (Percehellet & Sharma, 1980). It was proposed that adrenaline induces platelet aggregation by acting on 12-adrenoceptors, inhibiting adenylate cyclase, and decreasing cyclic AMP.…”