Laboratory Investigation

Kidney International (1979) 15, 463–472; doi:10.1038/ki.1979.62

Action of serotonin (5-hydroxytryptamine) on cyclic nucleotides in glomeruli of rat renal cortex

Sudhir V Shah1, Thomas E Northrup1, Yvonne S F Hui1 and Thomas P Dousa1

1Nephrology Research Laboratories, Department of Internal Medicine, Division of Nephrology, and the Department of Physiology and Biophysics, Mayo Clinic and Foundation, Rochester, Minnesota

Correspondence: Dr T P Dousa, Mayo Clinic & Foundation, 921 B Guggenheim Bldg., Rochester, Minnesota 55901, USA

Received 6 September 1978; Revised 19 October 1978.

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Abstract

Action of serotonin (5-hydroxytryptamine) on cyclic nucleotides in glomeruli of rat renal cortex. Serotonin (5-hydroxytryptamine) is known to influence glomerular function and may have an important role in the pathogenesis of glomerulopathies. Because serotonin acts in nonrenal tissues through mediation of cyclic nucleotides, we investigated in vitro its effect on cAMP and cyclic guanosine monophosphate (cGMP) in tissue slices and isolated glomeruli from rat kidney. Serotonin increased cAMP 161 plusminus 35% but not cGMP in renal cortex; it had no effect on cyclic nucleotides in medulla and papilla. In isolated glomeruli, serotonin elicited a dose-dependent (in the range of 10-7 to 10-4 M) increase in cAMP; the maximum increase over basal values was 376 plusminus 45%. Serotonin increased cAMP either in the presence or in the absence of a cAMP phosphodiesterase inhibitor. In tubular fraction, serotonin elevated cAMP to a much lesser degree (82 plusminus 15%). Neither in glomeruli nor in tubules did cGMP concentrations change in response to serotonin, but carbamylcholine, a known cGMP agonist, significantly increased cGMP concentrations. The increase in cAMP in response to serotonin was blocked (>85% inhibition) by equimolar concentrations of serotonin antagonists methysergide and cinanserine. Results of this study demonstrate that interaction of serotonin with receptors in the kidney, particularly in the glomeruli, cause a striking increase in cAMP concentrations without detectable changes in cGMP concentrations. These findings suggest that serotonin, either synthesized in the kidney or released locally from platelets aggregated in glomeruli (for example, in association with immu-nopathologic injury) may exert or modulate its physiologic or pathologic effects via mediation of cAMP.

Action de la sérotonine (5-hydroxytryptamine) sur les nucléotides cycliques des glomérules du cortex rénal du rat. Il est connu que la sérotonine (5-hydroxytryptamine) influence la fonction glomérulaire et peut avoir un rôle important dans la pathogénie des glomérulopathies. Puisque la sérotonine agit sur d'autres tissus que le rein par l'intermédiaire des nucléotides cycliques, nous avons étudié son effet in vitro sur le contenu en cAMP et cGMP des tranches de rein et des glomérules isolés du rein de rat. La sérotonine augmente cAMP 161 plusminus 35%, mais pas cGMP du cortex rénal. Elle n'a pas d'effet sur les nucléotides cycliques de la médullaire et de la papille. Dans les glomérules isolés la sérontonine détermine une augmentation de cAMP dose dépendante (de 10-7 à 10-4 M), l'augmentation maximale est de 376 plusminus 45% par rapport à la valeur basale. La sérotonine augmente cAMP aussi bien en présence qu'en l'absence d'inhibiteur de la cAMP phosphodiestérase. Dans les fractions tabulaires la sérotonine n'augmente cAMP qu'à un moindre degré (82 plusminus 15%). La sérotonine n'augmente cGMP ni dans les glomérules ni dans les tubules mais la carbamylcholine, un agoniste connu de cGMP augmente celui-ci significativement. L'augmentation de cAMP en réponse à la sérotonine est bloquée (inhibition supérieure à 85%) par des concentrations équimolaires des antagonistes méthysergide et cinansérine. Les résultats de ce travail démontrent que l'interaction de la sérotonine avec les récepteurs rénaux, particulièrement glomérulaires, détermine une augmentation importante de cAMP sans modification détéctable de cGMP. Ces constatations suggèrent que la sérotonine, qu'elle soit synthétisée dans le rein ou libérée localement par des aggrégats plaquettaires formés dans les glomérules (c'est à dire en association avec une lésion immunopathologique), peut exercer ou moduler ses effets physiologiques ou pathologiques par l'intermédiaire de cAMP.

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