Metabolism of iodomethane in the rat

1. The LD(50) of iodomethane orally administered to rats is 76mg./kg. body wt. but repeated daily doses of 30-50mg./kg. body wt. are without effect. 2. Oral doses of iodomethane to rats are rapidly converted into S-methylglutathione in the liver, and S-methylglutathione is excreted in the bile. 3. The conjugation process has been reproduced in vitro and shown to be enzymically catalysed. 4. S-Methylglutathione is degraded to S-methylcysteine by kidney homogenates. 5. Only a small proportion of a dose of iodomethane or of S-methylcysteine is excreted as compounds related to methylmercapturic acid. 6. Paper chromatography of extracts of livers from normal and dosed rats supports the view that GSH is the predominant non-protein thiol present.     

Calcitonin and CGRP block bombesin- and substance P-induced increases in airway tone

Calcitonin gene-related peptide (CGRP) and calcitonin (C) are two peptides that are cocontained and probably coreleased with the potent bronchocontrictors, bombesin (B) and substance P (SP), within the lung. Although CGRP and C have a wide intrapulmonary distribution, their actions have not been well defined. By the use of a computerized lung mechanics analyzer, changes in response to 10-min infusions of these agents were measured in spontaneously breathing, anesthetized guinea pigs. Infusion of 0.3 nmol.kg-1.min-1 CGRP and 2 nmol.kg-1.min-1 C caused little change in lung mechanics. Infusion of 0.06 nmol.kg-1.min-1 B and 0.3 nmol.kg-1.min-1 SP caused a marked increase in inspiratory, expiratory, and total pulmonary resistance (RT), from base-line values (P less than 0.02), with a maximal effect at 10 min postinfusion (PI) [RT = 326 +/- 20% (SE) (B), 490 +/- 73% (SP)]. Coinfusion of C or CGRP with B or SP at the above concentrations caused a marked reduction in SP - [RT = 189 +/- 28% (C), 142 +/- 16% (CGRP) at 10 min PI] and B - [RT = 157 +/- 18% (C), 158 +/- 10% (CGRP) at 10 min PI] induced changes in resistance (P less than 0.015). The mode of action of C and CGRP is unknown, but these peptides may antagonize the effects of B and SP via autonomic pathways by interfering with B- or SP-induced changes in intracellular calcium concentrations or by increasing intracellular cAMP levels by binding to specific cellular receptors linked to adenylate cyclase.