engleski

Signalling promiscuity of the metabotropic neurotransmitter receptors: are there any functional consequences?

The majority of neurotransmitter receptors belong to the superfamily of G-protein coupled receptors and are promiscuous in regard to their intracellualr signalling. (1) The simultaneous coupling implies activation of at least two different signalling pathways at the same time. Our knowledge about functional significance of this signalling diversity is restricetd to a limited number of cases. (2) The alternative coupling implies that a particular receptor, in a particular cell, may switch from one to another major signalling system. Studying the influence of adrenergic innervation on adrenal gland, we observed that stimulation of beta2-adrenergic receptors in hte fresh rat adrenal cortices induced cAMP accumulation, which was an expected signalling event. Unexpectedly, however, the effect of beta2-stimulation on cAMP levels in cortices remaining following unilateral adrenalectomy was completely opposite - beta2 stimulation lowered cAMO levels. At the same time, beta2 agonists stimulated and beta2 antagonists inhibited adrenal growth induce by the operation, while they had no effect on the adrenal growth in animals with both organs in situ. Regarding the signalling events, these results resemble the observations by Daaka et al in vitro (nature 1997, 390, 88-91) and indicate that an alternative coupling of beta2 receptros to Gs (prior to unilateral adrenalectomy) and Gi proteins (following the operation) may have occurred. Similar phenomena, but regarding muscarinic receptors and phosphoinositide signalling we observed in the rat ovary. Briefly, following hemigonadectomy the ovarian muscarinic receptros stimulated organ growth and were coupled to PI hydrolisis, while priot to the operation they were not coupled to PI signalling and did not influence ovarian growth. The temporal correspondence between the signalling witch and the occurrence of mitogenic effect to two investigated receptors suggests that the receptor function might have changed, as well.

neurotransmitters; receptors; signalling

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