engleski

Mitogenic activity of neurotransmitter receptors

Although the first evidence of the dopamine receptor-regulated proliferation of the pituitary prolactin-secreting cells was published in mid-seventies (Loyd et al. (1975) Nature 255: 497), its conceptual significance had remained overlooked for almost two decades. Namely, it is only recently that numerous studies have appeared showing that neurotransmitters acting through metabotropic receptors directly influence cell proliferation in vitro (reviewed in Trkulja et al. (1996) Period Biol 98: 17). In contrast to that only limited amount of data support mitogenic activity of neurotransmitter receptors in vivo. In our recent investigation of compensatory growth of the rat ovary and adrenal gland we found evidence that these phenomenons are mediated through muscarinic and beta-adrenergic receptors, respectively. For example, while splanchnecotomy or chemical sympathectomy (guanethidine or reserpine) and beta-adrenergic antagonists inhibited adrenal compensatory growth (evidenced by changes of the organ wet weight, protein content and total RNA and DNA contents). alfa-adrenergic and dopaminergic drugs were ineffective. The effects of sympathectomy and beta-antagonists were reversed by beta-agonists. In ovary bilateral abdominal vagotomy, muscarinic antagonists and cholinergic ovarian denervation (locally applied botulinum-toxin type A) inhibited compensatory ovarian growth. The effects of vagotomy, cholinergic denervation and muscarinic antagonists were antagonised by muscarinic agonists. Summarizing literature data on the in vivo evidence of neurotransmitter involvement in cell proliferation, together with our own results, it seems that neurotransmitters affect cell proliferation primarily when it is accelerated. In contrast, a world-wide, long-lasting experience with chronic medical usage of drugs affecting various neurotransmitter receptors suggests that neurotransmitters poorly, if at all, influence cell proliferation in an adult organism. Thus, a question arises: could it be that a particular neurotransmitter receptor, under certain circumstances, is able to switch its cell proliferation-regulating function on and off?

mitogenic; neurotransmitter receptors; ovariectomy

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