Histological and biochemical study on the effect of the neuropeptide [substance P] and its antagonist [spantide] on the lymphoid tissue of the lung and spleen of rats

The role of substance P in immune regulation has been reported by numerous studies, however it is complex and not fully elucidated. This study focused on its role in the mediation of release of cytokines and immunoglobulins and initiation of proliferative changes in the lymphoid tissue of the lung and spleen. Ninety rats were divided into three groups, each of thirty: Group I was injected with endotoxin free water [as control], Group II was injected with substance P and Group III was injected with substance P and spantide. Fifteen rats from each group were sacrificed after two hours and the other 15 after one week. The levels of interleukins I and 6 and immunoglobulins G and M were determined. Histological examination was performed for the spleen and lung revealing that the proliferation of the lymphoid tissue in both organs was more marked in the group sacrificed after one week. Interleukins I and 6 and immunoglobulins G and M showed significant increase in group II as compared with group I and III after two hours of injection as well as after one week. These findings suggested that the substance P-mediated release of interleukins I and 6 with production of immunoglobulins G and M and the proliferation of lymphoid tissue of the lung and spleen can be partially inhibited by spantide

Inflammatory responses induced by substance P in rat paw.

Substance P (SP) injection in the plantar region of rat hind paw caused a dose related inflammation, which reached a peak within 10 min of injection and declined after 60 min. Low doses (0.25-0.063 mg/kg) of SP-antagonists like (D-Pro2, D-Trp7,9)-SP and (D-Pro2, D-Phe7, D-Trp9)-SP pretreatment significantly inhibited the SP induced paw oedema, while higher doses (0.5-1 mg/kg) showed agonistic effects. Pretreatment with diphenhydramine alone or along with low doses of SP-antagonists was highly significant in blocking this inflammation, the latter combination being more effective than the former. Pretreatment with acute capsaicin produced a synergestic effect on SP induced paw oedema, while pretreatment with chronic capsaicin significantly inhibited this SP induced paw oedema. The results indicate involvement of histamine and possible therapeutic importance of capsaicin in SP mediated inflammatory type of responses.

Substance P injected into the medial preoptic area inhibits sodium, potassium and water urinary excretion: putative modulation of the cholinergic system

Substance P (SP, 1.5 nmol) injected into the medial preoptic area (MPOA) of conscious, unrestrained, water-loaded male rats induced a significant decrease in urinary sodium, potassium and water excretion. In contrast, a significant natriuretic effect was observed after injection of 0.3 nmol of a specific competitive SP antagonist ([D-Pr**2, D-Trp**7,**9]-substance P). SP partially blocked the carbachol-induced natriuresis in a time-dependent manner. These data indicate a tonic inhibitory action of SP on sodium excretion and suggest a putative modulatory action of SP on the cholinergic system