Induction of Responsiveness of Rat Diaphragm to Ovine Growth Hormone after Administration of Reserpine

Summary

The diaphragm of the pituitary intact rat is insensitive to the insulin-like effects of growth hormone unless weanling animals are used, and even then these effects are not achieved reliably. We report here that an intraperitoneal injection of reserpine is able to induce consistent responsiveness to ovine growth hormone (oGH) in hemidiaphragms from 20-27 day old rats as assessed by stimulation of ³H-AIB transport and ¹⁴C-phenylalanine incorporation into protein. Maximal stimulation of ³H-AIB transport (∼ 40%) can be elicited by addition of oGH (5 μg/ml) to hemidiaphragms after a 2 mg/kg injection of reserpine given 5 h prior to sacrifice. The degree of stimulation does not alter significantly if the rats are sacrificed 3, 5 or 12 h after administration of reserpine, although it decreases by 24 h. Administration of reserpine 3 h before sacrifice also leads to a 50% increase in ¹⁴C-phenylalanine incorporation into protein in rat diaphragms in response to the addition of oGH (5 μg/ml). The induced sensitivity to oGH is not due to inhibition of GH secretion by reserpine as demonstrated by RIA of plasma GH.

Addition of a monoclonal antibody to the GH receptor (MAb 263) did not result in a stimulation or inhibition of ³H-AIB uptake or stimulation of protein synthesis in reserpinized rat hemidiaphragms.

These results suggest that reserpine can induce tissue responsiveness in rats 20-27 d. o. independent of plasma GH levels. Our results also imply that the type 1 GH receptor of Barnard, Bundesen, Rylatt and Waters (1985) does not mediate the insulin like actions of GH on rat diaphragm.

Key words

Reserpine - Rat Hemidiaphragm - Plasma rGH - Monoclonal Antibody - Receptor