Proteína relacionada con la hormona paratiroidea: efectos autocrinos y paracrinos en los vasos sanguíneos y en el glomérulo renal / Protein related to parathyroid hormone: autocrine and effects of blood vessels and renal glomeruli

La hormona paratiroidea (PTH) y la proteína relacionada con la PTH (PTHrP) producen efectos biológicos similares a través del receptor PTH/PTHrP. Poco se sabe del papel fisiológico de la PTHrP, que inicialmente se identificó como el agente responsable de la hipercalcemia asociada a enfermedades malignas. Aunque esta proteína se produce ampliamente en diferentes tejidos, su concentración se encuentra debajo de los límites de detección, hecho que sugiere que en circunstancias fisiológicas actúa en forma autocrina o paracrina. Se han descrito algunas diferencias en los efectos de ambas proteínas posiblemente relacionados con la existencia de diferentes receptores. En este sentido, recientemente se ha descrito un receptor específico para la PTH, el receptor PTH-2. Estudios recientes han demostrado la expresión del receptor PTH/PTHrP y de la PTHrP en el glomérulo renal. Además, existen datos que muestran un efecto directo de PTH y PTHrP sobre el flujo plasmático renal y la filtración glomerular. La PTHrP posee las características de una proteína multifuncional, incluyendo efectos proliferativos sobre las células mesangiales, y se especula que tenga un papel importante en la fisiología y fisiopatología renales (AU)

Analgesic activity of the novel COX-2 preferring NSAID, meloxicam in mono-arthritic rats: central and peripheral components.

OBJECTIVE AND DESIGN: To study the characteristics and site of the analgesic action of meloxicam. SUBJECTS: Adult female Wistar rats. TREATMENT: Monoarthritis was induced (for behavioural studies) by injection of complete Freund's adjuvant into the ankle. Meloxicam was given for 5 days (0.1-4 mg/kg/ day i.p.). Inflammation of the knee or paw (for electrophysiology) was induced with carrageenan. Meloxicam was given i.v. (4-64 mg/kg). METHODS: Rats were tested daily for joint hyperalgesia, and hindlimb posture (behaviour). At post-mortem, joint stiffness, oedema and gastric lesions were assessed. In anaesthetised rats, nociceptive reflex responses to stimulation of the paw were compared (electrophysiology). Statistics were performed using one-way analysis of variance. RESULTS: Meloxicam reduced swelling and stiffness of the inflamed joint, joint hyperalgesia (ID50 = 0.4 +/- 0.4 mg/kg/ day) and spontaneous pain-related behaviour. It also inhibited peripherally mediated reflex responses to stimulation of inflamed tissue (ID50 = 7.6 +/- 0.8 mg/kg.i.v.) without affecting centrally mediated reflexes. CONCLUSIONS: Systemic meloxicam produces analgesia largely via peripheral mechanisms. The rapidity of its actions indicates a direct effect on sensitised nociceptors.

Irritation of the anterior segment of the eye by ultraviolet radiation: influence of nerve blockade and calcium antagonists.

The aim of this investigation was to determine the influence on anterior segment inflammation elicited by UV radiation, of ocular denervation and pharmacological blockade of sensory nerve fibers with capsaicin, tetrodotoxin and calcium antagonists. Both eyes of pigmented rabbits were exposed for 5 min to UV radiation (254 nm); 24 h later, inflammatory signs were evaluated by biomicroscopy of the corneal epithelium, the stroma and the endothelium and scored from 0 to 4. Conjunctival vasodilation and miosis were also assessed. Two weeks before UV exposure, a group of rabbits received a retrobulbar injection of ethanol or of 1% capsaicin. Intact, capsaicin-treated and alcohol-denervated animals were treated topically, prior to UV exposure, with tetrodotoxin (0.78 mM) and the calcium antagonists diltiazem (1-28 mM) and nifedipine (10 mM). UV radiation produced at 24 h signs of corneal irritation, conjunctival hyperemia, miosis and elevated protein content of the aqueous humor. Retrobulbar injection of 99% alcohol or 1% capsaicin did not diminish significantly the inflammation of tissues directly exposed to UV radiation, although extension of inflammatory signs to unaffected areas was prevented. Pre-treatment of normal and denervated eyes with diltiazem attenuated UV-induced eye irritation signs at concentrations of 10 mM or over. The effect was less pronounced with tetrodotoxin and was not obtained with nifedipine. These findings suggest that the contribution of a neurogenic mechanism to anterior segment inflammation induced by UV exposure is modest. They also show that high concentrations of diltiazem, but not of nifedipine, effectively reduced inflammation of the anterior segment of the eye evoked by UV radiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of capsaicin-induced ocular pain and neurogenic inflammation by calcium antagonists.

PURPOSE: To examine whether blockade of chemosensitivity of corneal nociceptors by Ca2+ antagonists decreases pain and irritation induced by capsaicin. METHODS: In adult rabbits, the number of lid-squeezing movements and the degree of palpebral opening, miotic response, and conjunctival vasodilation evoked by a bilateral instillation of 30 microliters of capsaicin (33 mM) were measured at different times (up to 5 hours) after the drug. Irritative responses to capsaicin in eyes pretreated with diltiazem, verapamil, or nifedipine were compared with those that received only the vehicle. Protein content in aqueous humor was also measured at the end of the experiment. RESULTS: Diltiazem at doses of 1 to 28 mM, administered 15 minutes before the application of capsaicin, significantly decreased scratching movements, conjunctival hyperemia, closure of the eye, and elevated aqueous protein concentration induced by capsaicin; however, it did not significantly reduce miosis. Nifedipine (2.8 and 10 mM) diminished the number of scratching movements but not other inflammatory parameters, whereas verapamil (2.8 and 10 mM) was totally ineffective in attenuating ocular signs of irritation produced by capsaicin. CONCLUSIONS: These results suggest that by lowering capsaicin-induced neural activity in nociceptive terminals, diltiazem decreases pain and neurogenic inflammation and may be useful as both an analgesic and an antiinflammatory agent in the eye.