The effect of calcium channel blockers and calmodulin inhibitors on the macrophage factor-stimulated synthesis of collagenase by rabbit chondrocytes

Nolan, Joseph C.; Gathright, C E; Wagner, Larry E.

doi:10.1007/bf01969097

Cited by 4 publications

(2 citation statements)

References 29 publications

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“…3-6 fM) significantly exceeded its IC50 (0.5 /tM) in vitro, this difference may reflect limited cellular permeability to calmidazolium. Furthermore, the concentration required to inhibit receptor recycling in reticulocytes was comparable with dosages reported elsewhere to inhibit calmodulin-dependent processes in intact cells [45][46][47][48][49].…”

Section: Discussionsupporting

confidence: 81%

Calmodulin dependence of transferrin receptor recycling in rat reticulocytes

Grasso

Bruno

Yates

et al. 1990

Biochemical Journal

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Kinetic analysis of transferrin receptor properties in 6-8 day rat reticulocytes showed the existence of a single class of high-affinity receptors (Kd 3-10 nM), of which 20-25% were located at the cell surface and the remainder within an intracellular pool. Total transferrin receptor cycling time was 3.9 min. These studies examined the effects of various inhibitors on receptor-mediated transferrin iron delivery in order to define critical steps and events necessary to maintain the functional integrity of the pathway. Dansylcadaverine inhibited iron uptake by blocking exocytic release of transferrin and return of receptors to the cell surface, but did not affect transferrin endocytosis; this action served to deplete the surface pool of transferrin receptors, leading to shutdown of iron uptake. Calmidazolium and other putative calmodulin antagonists exerted an identical action on iron uptake and receptor recycling. The inhibitory effects of these agents on receptor recycling were overcome by the timely addition of Ca2+/ionomycin. From correlative analyses of the effects of these and other inhibitors, it was concluded that: (1) dansylcadaverine and calmodulin antagonists inhibit iron uptake by suppression of receptor recycling and exocytic transferrin release, (2) protein kinase C, transglutaminase, protein synthesis and release of transferrin-bound iron are not necessary for the functional integrity of the iron delivery pathway, (3) exocytic transferrin release and concomitant receptor recycling in rat reticulocytes is dependent upon Ca2+/calmodulin, (4) dansylcadaverine, dimethyldansylcadaverine and calmidazolium act on iron uptake by interfering with calmodulin function, and (5) the endocytotic and exocytotic arms of the iron delivery pathway are under separate regulatory control.

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Section: Discussionsupporting

confidence: 81%

Calmodulin dependence of transferrin receptor recycling in rat reticulocytes

Grasso

Bruno

Yates

et al. 1990

Biochemical Journal

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“…In rabbit articular chondrocytes, the Ca2+ channel blockers nifedipine, verapamil and diltiazem had no effect on collagenase synthesis. However, inhibitors of internal Ca2+ movement do inhibit collagenase synthesis [30], suggesting that [Ca2+] is involved in the regulation of collagenase biosynthesis in chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

The substance P fragment SP-(7-11) increases prostaglandin E2, intracellular Ca2+ and collagenase production in bovine articular chondrocytes

Halliday

McNeil

Betts

et al. 1993

Biochemical Journal

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Substance P (SP) is found in increased concentrations in inflamed joints and is believed to play a role in joint pathology. Culture of bovine articular chondrocytes with SP or with the related mammalian tachykinins neurokinin A or B (NKA or NKB) produced no effect on prostaglandin E2 (PGE2) or collagenase production. However, the C-terminal fragment of SP, SP-(7-11), increased PGE2 and collagenase production at concentrations greater than 1 microM. The N-terminal fragments SP-(1-4) and SP-(1-6) had no effect on PGE2 or collagenase production. In addition, SP-(7-11), but not intact SP, SP-(1-4), SP-(1-6), SP-(8-11) or SP-(9-11), nor the tachykinins NKA and NKB, caused an increase in the intracellular calcium concentration as measured by the fluorescent dye Fura-2. The maximal change in intra-cellular calcium induced by 10 microM SP-(7-11) was 140 +/- 30 nM. We postulate that cleavage of SP by neutral endopeptidases which are present in the synovial fluid and which yield SP-(7-11) may be of biological importance in chondrocyte-mediated cartilage pathology.

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