The chronically reserpine (RES) treated rat is used as an animal model for cystic fibrosis (CF) because it exhibits functional, neural and morphologic alterations similar to those seen in CF. Adrenergic dysfunction, seen in the RES model may also occur in CF; cholinergic dysfunction may also exist, but the capability of the cholinergic nerve to salivary glands to respond to electrical stimulation has not been tested. This is important also since parasympathetic stimulation of nerve and receptors does not always give the same results. The adrenergic dysfunction is a result of the depletion of NE induced by RES. NE depletion may be responsible for many functional changes, including increase in glandular concentration of calcium. In fact, if the depletion of NE is critical for elevation in [Ca] to occur, similar increase in [Ca] should follow any sympathectomy, not just that induced by chronic RES treatment. Thus, [Ca] of salivary glands will be examined after a dose of 6 hydroxydopamine (6 OHDA), guanethidine or after surgical sympathectomy. Moreover, since NE depletion occurs within 24 hr after each drug, the chronic RES regimen may be replaced by the single dose regimen, possibly even with lower dosage. Comparisons will be made between effects of single doses of such drugs and those produced by the chronic RES regimen. On the other hand, the increase in glandular [Ca] may no be explicity related to NE since it is found also with drugs that presumably do not deplete NE. The cause of the increase in [Ca] will be sought. CF fibroblasts have been shown to have reduced levels of Mg++ Ca++ ATPase and mitochondria of these cells accumulate increased amounts of Ca++. Therefore, the cause of the increase in [Ca] with RES may be a deficiency in calcium transport related to altered Mg++ Ca++ ATPase in the glands, a condition which in turn stems from the deficiency in NE. The glands of rats sympathectomized by RES, 6 OHDA, guanethidine, or surgical sympathectomy will be examined for Mg++ Ca++ ATPase activity. These interrelationships will be examined using biochemical methods for analysis of NE, Mg++ Ca++ ATPase, and calcium. the physiological status of the gland, including denervation-induced degeneration secretion and supersensitivity will also be monitored by examination of functional modalities (volume, Na, K, Cl, amylase activity). This work should aid in elucidation of the pathogenesis of CF.
| Schneyer, C A; Cheung, H (1987) Ca-ATPase activity in salivary glands of rats treated with reserpine, isoproterenol, terbutaline or dobutamine. Arch Oral Biol 32:445-7 |
| Jirakulsomchok, D; Schneyer, C A (1987) Effects of saliva from chronically reserpinized rat on Na and K transport in perfused main excretory duct of submandibular gland of normal rat. Proc Soc Exp Biol Med 185:392-5 |
| Schneyer, C A (1986) Growth of rat salivary glands after terbutaline or dobutamine. J Oral Pathol 15:66-70 |
| Schneyer, C A (1985) Calcium and norepinephrine levels of rat salivary glands after terbutaline, dobutamine or isoproterenol. J Auton Nerv Syst 14:191-200 |
| Schneyer, C A; Yu, J H (1985) Developmental status of sympathetic innervation in relation to calcium accumulation by submandibular gland following reserpine, surgical sympathectomy or cyclocytidine. Proc Soc Exp Biol Med 179:143-6 |
