RESUMEN
Peptide histidine-isoleucine (PHI) and its human analogue peptide histidine-methionine (PHM) are members of a superfamily of structurally related peptides embracing, among others, pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), peptide histidine-valine (PHV), and helodermin. All the peptides display a pleiotropic biological activity. PHI, PHM, PHV and VIP are co-synthesized from the same precursor and share high levels of structural and functional similarity. These peptides may act through common receptors and are widely distributed throughout the body tissues (the central nervous system, gastrointestinal tract, respiratory system, and reproductive system); however, their role remains largely unknown. Changes in the levels of the peptides in the course of different diseases suggest their possible importance and usefulness in diagnostics. Moreover, the neurotrophic and neuroprotective properties of PHI suggest, by analogy to VIP or PACAP, its therapeutic potential in many neurodegenerative diseases, such as Alzheimer's and Parkinson's disease.
Asunto(s)
Péptido PHI/fisiología , Secuencia de Aminoácidos , Animales , Bovinos , Pollos , Peces , Humanos , Ratones , Datos de Secuencia Molecular , Enfermedades Neurodegenerativas/tratamiento farmacológico , Péptido PHI/química , Ratas , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria , Receptores de la Hormona Hipofisaria/metabolismo , Receptores de Péptido Intestinal Vasoactivo/metabolismo , Receptores de Tipo II del Péptido Intestinal Vasoactivo , Receptores de Tipo I del Polipéptido Intestinal Vasoactivo , Especificidad de la Especie , Porcinos , TurquíaRESUMEN
Vasoactive intestinal peptide (chicken form; chVIP), peptide histidine-isoleucine (porcine and rat forms; pPHI and rPHI), D-Phe(4) derivative of porcine PHI (D-Phe(4)-pPHI), peptide histidine-methionine (PHM; human PHI), and helodermin, were tested for their ability to stimulate cAMP production in [(3)H]adenine-prelabeled slices of chick cerebral cortex (CCx) and hypothalamus (HTh). The chVIP (0.1-3 microM) concentration-dependently and potently stimulated cAMP production in HTh and CCx; the responses observed after 3 microM of chVIP were comparable to those produced by 0.1 microM PACAP38. Helodermin (5 microM) moderately but significantly stimulated cAMP formation in both HTh and CCx, whereas pPHI, rPHI, PHM at 5 microM concentration only weakly affected cAMP production in CCx, and were inactive in HTh; D-Phe(4)-pPHI was inactive in both tissues. These data demonstrate that chVIP, PACAP, and to a lesser extent helodermin were capable of potently stimulating cAMP generation in the avian central nervous system. PHI-related peptides showed only weak or no activity, depending on the tissue.
Asunto(s)
Pollos , AMP Cíclico/biosíntesis , Péptido PHI/farmacología , Isoformas de Proteínas/farmacología , Péptido Intestinal Vasoactivo/farmacología , Animales , Radioisótopos de Carbono , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Hipotálamo/citología , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Masculino , Neuropéptidos/metabolismo , Neuropéptidos/farmacología , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/farmacología , Péptido PHI/metabolismo , Péptidos/metabolismo , Péptidos/farmacología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Receptores de Péptido Intestinal Vasoactivo/efectos de los fármacos , Receptores de Péptido Intestinal Vasoactivo/fisiología , Análisis de Secuencia de Proteína , Porcinos , Tritio , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
The Ca(2+)-dependent activation of retina-specific guanylyl cyclase (retGC) is mediated by guanylyl cyclase-activating proteins (GCAPs). Here we report for the first time detection of a 19 kDa protein (p19) with GCAP properties in extracts of rat retina and pineal gland. Both extracts stimulate synthesis of cGMP in rod outer segment (ROS) membranes at low (30 nM) but not at high (1 microM) concentrations of Ca(2+). At low Ca(2+), immunoaffinity purified p19 activates guanylyl cyclase(s) in bovine ROS and rat retinal membranes. Moreover, p19 is recognized by antibodies against bovine GCAP1 and, similarly to other GCAPs, exhibits a Ca(2+)-dependent electrophoretic mobility shift.
