RESUMO
Insulin-like growth factor (IGF)-I is a ubiquitously synthesized peptide that, along with IGF-II, acts via the IGF-R type I receptor. IGF-I and its receptor are expressed in the adrenal gland of humans and bovines, the secretion of which they seem to stimulate. As in humans and cows, the main glucocorticoid hormone secreted by guinea-pig adrenals is cortisol, and hence we have studied the adrenocortical effects of IGF-I in this species. In vivo experiments showed that prolonged IGF-I administration raised the plasma concentration of cortisol in both normal and dexamethasone/captopril-treated guinea pigs, thereby ruling out the possibility that IGF-I may act by activating the hypothalamic-pituitary-adrenal axis and the renin-angiotensin system. In vitro experiments demonstrated that IGF-I enhanced basal, but not maximally agonist [ACTH and angiotensin-II (Ang-II)]-stimulated, cortisol secretion from freshly dispersed guinea-pig inner adrenocortical cells. The IGF-I immuno-neutralization suppressed the IGF-I secretagogue effect, without altering the cortisol response to both ACTH and Ang-II. IGF-I raised cyclic-AMP and inositol triphosphate release from dispersed guinea-pig cells, and the effect was reversed by the adenylate cyclase inhibitor SQ-22536 and the phospholipase-C (PLC) inhibitor U-73122. SQ-22536, U-73122, the protein kinase (PK) A inhibitor H-89 and the PKC inhibitor calphostin-C decreased by approximately 50% the cortisol response of dispersed cells to IGF-I, and the combined exposure to SQ-22536 and U-73122 abolished it. We conclude that IGF-I stimulates glucocorticoid secretion from guinea-pig adrenocortical cells, acting via selective receptors coupled to both the adenylate cyclase/PKA- and PLC/PKC-dependent signaling cascades.
Assuntos
Córtex Suprarrenal/citologia , Córtex Suprarrenal/fisiologia , Hidrocortisona/metabolismo , Fator de Crescimento Insulin-Like I/administração & dosagem , Fator de Crescimento Insulin-Like I/farmacologia , Córtex Suprarrenal/metabolismo , Animais , Captopril/farmacologia , AMP Cíclico/análise , AMP Cíclico/metabolismo , Dexametasona/farmacologia , Cobaias , Hidrocortisona/análise , Hidrocortisona/sangue , Técnicas In Vitro , Fosfatos de Inositol/análise , Fosfatos de Inositol/metabolismo , Masculino , Zona Fasciculada/fisiologia , Zona Reticular/fisiologiaRESUMO
Effect of prolonged administration of substance P on the plasma cortisol level in the albino rats has been investigated. An inhibitory impact on intact individuals and a stimulatory effect in pharmacologically annulled rats has been observed. It is concluded that in normal conditions substance P presumably acts as a preventive agent for any excess secretion of cortisol while during stress or disturbed HPA or RAS conditions, it stimulates the secretion of cortisol. An intraglandular modulatory role of substance P has been suggested.
Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Hidrocortisona/sangue , Neurotransmissores/farmacologia , Substância P/farmacologia , Glândulas Suprarrenais/metabolismo , Animais , Hidrocortisona/antagonistas & inibidores , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Injeções Subcutâneas , Ratos , Estresse Fisiológico/patologia , Estresse Fisiológico/prevenção & controle , Substância P/administração & dosagemRESUMO
The present study was undertaken to assess the toxicity of acid alone and two different sublethal concentrations of aluminium, (25% and 75% dose of 96 hr LC50 value in acidified soft water of pH 5) on red blood cells of a stenohaline catfish, C. batrachus for an acute exposure of 5 days. The scanning electron microscopic studies on all the three treated groups revealed several kinds of erythrocyte alterations and modifications with abnormal morphology. These included abnormal surface-wrinkling accompanied with excessive roughness on the membrane, erythrocytes with surface granulation in higher dose and finally the appearance of morphologically abnormal forms, the codocyte (target cell) and the stomatocyte. The results suggest that abnormality in the shape of erythrocytes could be linked to altered surface membrane area to volume ratio, decrease in cytoplasmic volume owing to reduced Hb content or increase in the amount of water content within the cell resulting from osmotic disequilibrium. In this context, the abnormal surface membrane morphology could be attributed to cytoskeleton fragility and defects in structural proteins. Further, the acid group exhibited a striking behavior of cellular adhesion and bonding to adjoining cell surfaces, culminating in several bunches which thereby reduces the surface area for gaseous exchange and could produce blocking effect while flowing through microcirculation.