Electrolyte and protein secretion by the perfused rabbit mandibular gland stimulated with acetylcholine or catecholamines

Abstract

A method is described for the isolation and vascular perfusion in vitro of the rabbit mandibular gland. The perfusate is a physiological salt solution containing glucose as the only metabolic substrate. During perfusion with solutions containing acetylcholine [A], the gland secretes vigorously at a rate and in a manner similar to that seen in vivo. Although the gland becomes edematous during perfusion, the extent of this edema appears to have no influence on secretory ability: the perfused glands were capable of functioning for at least 4 h and often for more than 6 h. A evoked a small secretory response at a concentration of 8 .times. 10-9 M and a maximum response at 8 .times. 10-7 M. Eserine (2 .times. 10-5 M) evoked secretory responses comparable to those evoked by A in a concentration of 8 .times. 10-9 M. Secretion, whether unstimulated or evoked by A or eserine, could be blocked completely by atropine. During prolonged stimulation with A, the fluid secretory response declined rapidly over a period of about 15 min from an initial high value to a much lower plateau value. After 3 or more hours of stimulation, the secretory response began once more to decline, this time towards zero. If, before the 2nd period of decline begins, stimulation is interrupted for about 30 min, the gland recovers its initial responsiveness to further stimulation with A. The Na, K, Cl and HCO3 concentrations and the osmolality of A evoked saliva exhibited flow-dependency similar to that seen in vivo. The concentrations of Na and Cl, but not K and HCO3, increased by about 25 mM during periods of prolonged stimulation with A even though the salivary secretory rate was constant. The concentrations of K and HCO3, but not Na and Cl, increased progressively as the concentration of infused A was increased. Salivary protein secretion increased with increasing A concentrations to a greater extent than did fluid secretion. During continuous stimulation, the rate of protein secretion fell off much faster than the rate of fluid secretion. The .beta.-adrenergic agonist isoproterenol evoked a fluid secretory response only equal to about 5% of that evoked by A, but still the response declined during continued stimulation. The electrolyte composition of isoproterenol-evoked saliva was vastly different from that evoked by A, being particularly rich in K and HCO3. The isoproterenol-evoked salivary was also extremely rich in protein so that the total protein secretion evoked by isoproterenol was much greater than that evoked by A. The .alpha.-adrenergic agonist phenylprine was without stimulatory effect on salivary fluid secretion and caused a reduction in the secretory response to A. The drug had little or no effect on the electrolyte content of A evoked saliva and appeared to reduce its protein content.