Jia-Huey Yu

Modification of dobutamine- and terbutaline-induced calcium and fluid secretion from rat salivary glands by atenolol and butoxamine

Saliva was elicited from rat salivary glands by terbutaline at i.p. doses of 1, 5, 10 and 25 mg/kg b.wt. but not by doses of 0.1 or 0.5 mg/kg b.wt. Dobutamine elicited no secretion at 1 or 2 mg/kg but did at 5, 10 and 25 mg/kg b.wt. At 5 mg/kg terbutaline evoked nearly maximal volumes but with dobutamine, volumes were small at this dosage. At dosages of 10 and 25 mg/kg volumes with the two agonists were similar for parotid, but with submandibular, the volumes evoked by dobutamine were nearly two times as high as those elicited by terbutaline. Mean [Ca] of parotid saliva was also similar at all dosages of dobutamine (approximately 12 mEq/liter) and generally similar at all dosages of terbutaline (11-15 mEq/liter). Mean [Ca] of dobutamine-elicited submandibular saliva was approximately 6, 7 and 8 mEq/liter at 5, 10 and 25 mg/kg b.wt, respectively. With parotid, [Ca] was approximately 10 mEq/liter at 1, 5 and 10 mg/kg b.wt. but increased to 16-18 mEq/liter at 25 mg/kg. The time course of calcium secretion is described for both agonists at each dosage. [Ca] of both glands was decreased 60 min after i.p. injection of 10 or 25 mg/kg doses of dobutamine or terbutaline but was not changed by 5 mg/kg doses. Administration of 10 mg/kg of atenolol, the selective beta 1 antagonist, 20 min prior to injection of a 10 mg/kg dose of either terbutaline (beta 2 agonist) or dobutamine (beta 1 agonist) blocked secretion from both glands, and prevented the usual agonist-induced reduction in glandular concentration of calcium. Butoxamine, on the other hand, did not modify effects of terbutaline on fluid secretion or depletion of glandular calcium; it did partially inhibit dobutamine-induced fluid and calcium secretion but not depletion of glandular calcium. The present data suggest that beta adrenoceptors of salivary glands are predominantly of the beta 1 subtype and that it is these that regulate calcium and fluid secretion. On the basis of the data with the antagonists, it is concluded that terbutaline activates beta 1 rather than beta 2 receptors since the beta 1 antagonist but not the beta 2 antagonist blocked secretory responses to terbutaline.

Effect of α- and β-adrenergic agonists on fluid and calcium secretion by rat salivary glands

Abstract The separate roles of ga- and β-adrenergic receptors in regulating fluid and calcium (Ca) secretion by rat salivary glands were examined using phenylephrine (PE), an adrenergic agonist that acts predominantly on ga-receptors, isoproterenol (ISO), an adrenergic agonist that acts predominantly on β-receptors, and PE and ISO in combination with β-adrenergic antagonist propranolol (PROP) and α-adrenergic antagonist phentolamine (PHENTO), respectively. PE evoked a greater volume of saliva from submandibular (SM) gland than from parotid (PA) gland, whereas ISO evoked a similar volume of saliva from both glands during 60-min of drug stimulation. PE even at a low dose had β-adrenergic effects on flow rate of salivary glands because pretreatment of rats with PROP (1 mg/kg) 20 min before PE (5 mg/kg, i.p.) stimulation resulted in a 4-fold reduction in total volume of PE-evoked PA saliva. Thus α-adrenergic receptors play a major role in fluid secretion by SM glands but play only a minor role in PA glands. ISO evoked SM and PA saliva with Ca concentration higher than that evoked by PE. ISO (25 mg/kg, i.p.) also had an effect on α-adrenergic receptors as well as β-adrenergic receptors. Although PHENTO did not significantly alter flow rate and volume of ISO-evoked PA or SM saliva, Ca concentration of ISO-evoked saliva was greatly potentiated by PHENTO. Total Ca output of ISO-evoked saliva from either gland was not significantly altered by PHENTO. Thus, in both salivary glands, activation of β-adrenergic receptors evoked saliva with a high concentration of Ca. ISO caused a marked decrease in glandular Ca concentration of both PA and SM whereas PE caused a marked depletion of glandular Ca concentration of SM but no depletion of Ca concentration of PA. PROP or PHENTO only slightly decreased ISO or PE-induced glandular depletion of Ca concentration of both glands. Thus, use of ISO or PE to delineate the specific role of α- or β-adrenergic receptors must take into account the affinities ISO and PE have for both types of adrenergic receptors of salivary glands.

Salivary Secretion Induced by Substance P

Abstract Secretion of fluid, ions, and amylase from parotid and submaxillary glands of rat, induced by intravenous injection of substance P (SP), was examined. The action of SP on salivary glands, like physalaemin, resembled that of cholinergic stimulation. While SP-evoked salivary flow from both glands was blocked by atropine, atropine did not modify composition of SP-evoked saliva. The present study suggests that salivary secretion and secretion of ions and amylase evoked by SP are mediated via SP-sensitive cholinergic receptors and specific SP receptors, respectively.

Prostaglandin E1 induced salivary secretion

PGE1 but not PGF2α at 500–1000 μg/kg induced a slow and sparse flow from the parotid and no flow at all from submaxillary glands. Composition of PGE1-induced parotid saliva was quite different from that evoked by any autonomic agonists. The present study suggests that PGE1 might act directly on parotid acinar cells.

Secretory responses to autonomic stimulation of rat salivary glands following reserpine treatment

The response to stimulation of the parasympathetic innervation to parotid or submandibular glands of reserpinized rats was altered from that of untreated rats. Thus, acute reserpinization, like other types of sympathectomy, resulted in increase in volume of parasympathetically-evoked parotid or submandibular saliva when comparison was made with evoked saliva from untreated glands. As norepinephrine is depleted by reserpine, there was no response to stimulation of sympathetic nerves to these reserpinized glands. Adrenergic receptors were normally activated by administration of autonomic agonists. Thus a single high dose of reserpine can cause the same effects as those induced by chronic administration of low doses of reserpine, i.e. a 3-fold increase in calcium (Ca) concentration of submandibular gland but no change in Ca concentration of parotid gland. Although sympathetic stimulation caused no change in Ca concentration of submandibular or parotid glands of reserpine (acute)-treated rats, stimulation with isoproterenol (25 mg/kg, i.p., 60 min) produced a 32-35 per cent decrease in glandular Ca concentration from that of unstimulated reserpinized glands. Glands of untreated rats showed a 52 per cent depletion after 60 min of isoproterenol stimulation; however, Ca output in parotid saliva from reserpinized rat for 60 min of stimulation was not changed from that of untreated rats, but that of submandibular saliva was two times greater. Ca concentration of submandibular saliva was unchanged during 60 min-stimulation of reserpine-treated rats, but that of untreated rats decreased.

Effects of varying frequency of parasympathetic nerve stimulation on flow rate and ion concentrations of rat submandibular saliva

Effects of adrenergic antagonists on chorda-evoked salivary secretion were studied. Flow rate, Ca and Na concentration of the chorda-evoked saliva were related to changes in frequency of stimulation of the chorda. Thus, as frequency of stimulation was increased, flow rate, Ca and Na concentrations increased. However, K concentration of nerve-evoked saliva was similar at all frequencies. Depletion of gland Ca concentration was also dependent on frequency of the stimulation; at the highest frequency, there was a greater depletion of gland Ca concentration than at lower frequencies. The data indicate that stimulation of the chorda tympani nerve elicits what can be called pure parasympathetic saliva, as neither phentolamine nor propranolol blocked chorda-evoked secretion.

Nerve-Stimulated Secretion of Calcium by Rat Submandibular Gland

Abstract The comparative effects of electrical stimulation of parasympathetic (chorda tympani nerve) and sympathetic innervation to the rat submandibular gland on calcium secretion were examined. The separate roles of α- and β-adrenergic receptors in the regulation of calcium secretion during sympathetic nerve stimulation were also determined. The present study shows that the parasympathetic and sympathetic innervations to rat submandibular gland have very different effects on [Ca] of saliva; the regulatory influence of the sympathetic is more prominent than that of the parasympathetic innervation; [Ca] of submandibular saliva evoked by chorda stimulation was about 25 times less than that of saliva evoked by sympathetic stimulation. However, since total volume of chorda-evoked submandibular saliva was about 20 times greater than that of sympathetically evoked saliva, the total output of calcium following stimulation of either autonomic branch was similar. Glandular depletion of calcium for both kinds of nerve stimulation was also similar. Comparison with previous studies on the rat parotid gland shows that the role of the parasympathetic innervation in regulation of [Ca] of saliva and glandular depletion of calcium differed in the two glands while that of the sympathetic innervation was generally similar for both submandibular and parotid glands. Calcium secretion from rat submandibular gland was decreased during sympathetic nerve stimulation in the presence of propranolol, a β-adrenergic blocker, while it was greatly increased when the sympathetic nerve was stimulated in the presence of phentolamine, an α-adrenergic blocker. Thus, it was concluded that with both glands β-adrenoceptors play the major role in the regulation of calcium secretion.

Postnatal changes in calcium and amylase of rat salivary glands, including calcium changes with senescence.

Postnatal changes occur in glandular Ca concentration of rat parotid and submandibular glands. At 4 days of age, Ca concentration was low in both glands (only one-third to one-half that of adults) and increased gradually with age. The pattern of change was generally similar for male and female rats, but in submandibular gland, adult levels of 9-10 m-equiv./kg were reached by weaning, whereas for parotid gland, a gradual increase in Ca concentration occurred with adult levels of 9-10 m-equiv./kg reached by 7 weeks of age. The pattern of change was the same whether Ca concentration was expressed per kg wet or dry weight albeit water content changed with age. The changes in Ca concentration of parotid paralleled the age-associated increases in amylase activity of parotid gland. Amylase activity of submandibular gland was much less than that of parotid and similarly low at all ages examined, and did not parallel the age-associated increases in Ca concentration. The regulatory role of the sympathetic innervation on glandular Ca concentration was examined by effecting surgical denervation of parotid and submandibular glands at 8 days of age, and then determining Ca concentration of the denervated glands at 32 days. A three-fold increase in Ca concentration, similar to that following acute sympathectomy in adults, occurred in submandibular gland but no change was seen in parotid. An unexpectedly high concentration of Ca was also found in submandibular (but not parotid) gland of old rats.

Effects of substance P on Na and K transport in perfused main submandibular duct of rat.

Abstract Substance P (2 and 4 μg/kg · min, iv) caused an inhibition of net efflux of Na and net influx of K in perfused main excretory duct of rat submandibular gland. These effects could not be blocked by atropine sulfate. The data suggest that substance P receptors are present in the duct cells and play a role in the regulation of transductal electrolyte transport.

Parasympathetically evoked parotid salivary secretion of chronically amitriptyline-treated rats

Treatment of rats with amitriptyline for 4 weeks significantly decreased flow rate of saliva elicited from parotid glands in response to electrical stimulation of the parasympathetic innervation but did not alter calcium concentration of such saliva. The mechanism of the dissociation between flow rate and calcium concentration of parasympathetically evoked saliva induced by amitriptyline treatment remains to be explored, and may not involve an amitriptyline induced reduction in acetylcholine release.