Further studies on the mode of action of calcitonin on isolated rat osteoclasts: pharmacological evidence for a second site mediating intracellular Ca2+ mobilization and cell retraction.

Alam, A; Bax, C; Shankar, V; Bax, B; Bevis, P; Huang, C; Moonga, B; Pazianas, M; Zaidi, M

Journal article

Further studies on the mode of action of calcitonin on isolated rat osteoclasts: pharmacological evidence for a second site mediating intracellular Ca2+ mobilization and cell retraction.

Abstract:: Calcitonin is a circulating polypeptide that inhibits bone resorption by inducing both quiescence (Q effect) and retraction (R effect) in osteoclasts. Two structurally related members of the calcitonin gene peptide family, calcitonin gene-related peptide (CGRP) and amylin, inhibit osteoclastic bone resorption selectively via the Q effect. In the present study, we have made measurements of cell spread area in response to the application of amylin, CGRP and a peptide fragment of CGRP, CGRP-(Val8Phe37). We found that, over a wide concentration range (50 pmol/l to 2.5 mumol/l), the selective Q effect agonists did not produce an R effect. Furthermore, the peptides, when used at a 50-fold higher molar concentration than calcitonin, did not antagonize calcitonin-induced cell retraction. Additionally, experiments designed to measure changes in the intracellular free calcium concentration ([Ca2+]i) in single osteoclasts revealed that, unlike calcitonin, the non-calcitonin Q effect agonists did not produce a rise in [Ca2+]i. The peptides were also unable to attenuate the peak rise in [Ca2+]i induced by calcitonin. The results support our hypothesis that the inhibitory activity of calcitonin on osteoclastic bone resorption is mediated by two sites which may or may not be part of the same receptor complex. One of these is the classical Q effect site coupled to adenylate cyclase via a cholera toxin-sensitive Gs. This site can be activated by nanomolar concentrations of calcitonin, amylin, CGRP or CGRP-(Val8Phe37). A novel R effect site, possibly coupled via a pertussis toxin-sensitive G protein to a [Ca2+]i elevating mechanism is predicted from this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Alam, A., Bax, C., Shankar, V., Bax, B., Bevis, P., Huang, C., Moonga, B., Pazianas, M., & Zaidi, M. (1993). Further studies on the mode of action of calcitonin on isolated rat osteoclasts: pharmacological evidence for a second site mediating intracellular Ca2+ mobilization and cell retraction. Journal of Endocrinology, 136(1), 7–15.

MLA Style

Alam, A, et al. “Further Studies on the Mode of Action of Calcitonin on Isolated Rat Osteoclasts: Pharmacological Evidence for a Second Site Mediating Intracellular Ca2+ Mobilization and Cell Retraction.” Journal of Endocrinology, vol. 136, no. 1, 1993, pp. 7–15.

Chicago Style

Alam, A, C Bax, V Shankar, et al. 1993. “Further Studies on the Mode of Action of Calcitonin on Isolated Rat Osteoclasts: Pharmacological Evidence for a Second Site Mediating Intracellular Ca2+ Mobilization and Cell Retraction.” Journal of Endocrinology 136 (1): 7–15.
Print