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C J Perec

Publications and source records attributed to C J Perec.

At least 19 recordsLinked to original sources
PubMed1990

Physiological role of alpha-adrenoceptors in salivary secretion.

The submaxillary gland (SM) of rat is innervated by both branches of the autonomic nervous system. Secretion is mediated by the activation of both muscarinic-cholinergic and alpha/beta adrenergic receptors. Studies of the relative affinity of pharmacological agonists and antagonists have warranted a subclassification of alpha adrenoceptors into types alpha 1 and alpha 2. Our studies involve an analysis of the physiologic role of both types of alpha adrenoceptors in salivary secretion. Dose response curves (DRC) to noradrenaline (NA) following administration of alpha adrenoceptor antagonists, i.e. prazosin (alpha 1 antagonist), yohimbine (alpha 2 antagonist) and phentolamine (alpha 1-alpha 2 antagonist) were constructed. Our results demonstrate that prazosin is 100 times more effective than yohimbine in blocking NA-induced salivary secretion. The alpha 2 agonist clonidine (10 micrograms/Kg) blocked the DRCs to methacholine, noradrenaline and substance P-but failed to modify the DRC to isoproterenol. Our results reveal that the subtypes of alpha adrenergic receptors play antagonistic roles in salivary secretion. Alpha 1 stimulation elicits profuse salivary secretion whereas alpha 2 stimulation inhibits salivary secretion induced by 3 different types of agonists, i.e. alpha 1, muscarinic-cholinergic and neurokininergic without affecting beta receptor mediated responses.

Animals↗
PubMed1990

Effects of intravenous ethanol on basal bile-pancreatic secretion in nonalcoholic and alcohol-fed rats.

In nonalcoholic (NA) and alcohol-fed rats (AF), intravenous-ethanol-induced percentage changes in bile-pancreatic-secretion (BPS) were evaluated, with and without gastric juice diversion (GJD) and with and without BPS duodenal recirculation (DR). Even with GJD, ethanol elicited a slight increase in BPS. These changes were greater in AF animals even when performed without GJD. When intravenous ethanol was given under conditions of GJD and DR, there were marked differences between the NA and AF animals in the ethanol-elicited post-plateau percentage changes of BPS. NA animals evidenced no significant difference from controls. But in the AF rats, ethanol triggered a marked and significant increase of flow, protein concentration, and output that became progressively greater in successive collection periods. It is postulated that without DR, and the resulting lack of negative duodeno-pancreatic reflexes (DPR), there occurs a change in reactivity to intravenous ethanol of the hypothalamic-bulbar nuclei (HBN) and in the mechanisms that modulate the flow of cholinergic impulses through the intrapancreatic ganglia (IPG). The postulated consequence is predominance (slight in NA rats receiving intravenous ethanol, greater in AF rats) in discharge of positive impulses from HBN and flowing unimpeded through the IPG to the "pancreon" units. In the NA animal with DR, ethanol may enhance BPS values, but in the AF rats, impairment of the negative DPR elicited by chronic alcohol intoxication might, after an acute intravenous ethanol injection, favor the discharge of positive impulses from the HBN flowing unimpeded through the IPG. In the AF rats also, ethanol would activate the nonnicotinic receptors of the neurons of the "antral," "duodenal," and "celiac" autonomic brains.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed1989

Potassium-evoked efflux of [3H]purines from the rat submaxillary gland.

1. Normal, atrophied and denervated submaxillary glands were incubated with [3H]adenine for 1 h. The accumulation of [3H]adenine, expressed as microCi/g tissue, did not differ significantly when the sympathetically denervated glands were compared with the control group. The radioactivity retained in both control and denervated tissues was also similar. 2. In atrophied glands 3H-accumulation as well as 3H-retention were 2-fold higher than these obtained in controls per unit weight, but 30% lower when expressed per gland. 3. The spontaneous efflux of radioactivity, expressed as fractional release, from normal, atrophied and denervated glands prelabelled with [3H]adenine was similar. 4. The outflow of radioactivity was enhanced by exposure of the tissues to 60 mM K+ during 2.5 min. 5. In all three groups, the purine release induced by K+ was the same. 6. Phentolamine 3.1 microM enhanced the K+-induced release of [3H]purine compounds in control and atrophied glands but not in denervated glands. 7. Propranolol 0.3 microM produced no changes among the three experimental groups. 8. Atropine 1 microM and phentolamine 3.1 microM plus atropine 1 microM did not modify the release of tritiated purine compounds in control and denervated glands. 9. Our results cannot discriminate between neuronal or non-neuronal elements as the source of purines released by depolarization but suggest that classical pharmacological tools such as phentolamine and atropine may affect purine metabolism in a complex fashion.

Adenine↗
PubMed1987

Interaction between amphetamine and alpha 2-postsynaptic adrenoreceptors in the rat submaxillary gland.

1 The interaction between amphetamine and the alpha 2-adrenoreceptor agonists, clonidine and guanabenz, was studied in the submaxillary gland of anaesthetised rats. 2 Low doses of clonidine (10 micrograms/kg) and guanabenz (10 micrograms/kg) inhibited the secretory responses induced by methacholine and substance P, respectively. 3 Amphetamine (300 micrograms/kg) antagonized the inhibitory effects of both alpha 2-agonists. This dose of amphetamine alone did not show sialagogic effects. 4 Atropine (1 micrograms/kg) diminished the secretory responses to methacholine as much as clonidine (10 micrograms/kg). Amphetamine did not modify the blockade by atropine. 5 Guanabenz (10 micrograms/kg) markedly decreased the secretory responses to substance P, an effect that was also prevented by amphetamine. 6 Reserpine pretreatment (5 mg/kg, i.p., 18 h) did not alter the effect of amphetamine. 7 These results indicate that the interaction between amphetamine and alpha 2-adrenoreceptor agonists is unrelated to the indirect effect of this amine and suggest a direct interaction between the drug and postsynaptic inhibitory alpha 2-adrenoreceptors.

Adrenergic alpha-Agonists↗
PubMed1986

Blockade of postsynaptic alpha 2-adrenoceptors enhances responses to mixed alpha 1/alpha 2-agonists in rat submaxillary gland.

The effects of selective blockade of alpha 2-adrenoceptors with idazoxan on salivary secretion elicited by several alpha-adrenoceptor agonists known to differ in their alpha 1/alpha 2 potency ratios were studied in the submaxillary gland. Doses of idazoxan ranging between 0.01 to 10 000 micrograms/kg did not produce secretion in anaesthetized rats. Idazoxan (3 micrograms/kg) effectively blocked the inhibitory action of clonidine, 10 micrograms/kg, on the responses to methacholine but did not change the sialagogic responses to either phenylephrine or isoprenaline. On the other hand, idazoxan enhanced the secretion elicited by other agonists known to have mixed alpha 1/alpha 2-agonistic properties. The degree of augmentation of the responses observed after alpha 2 blockade was: clonidine much greater than alpha-methyl-norepinephrine greater than norepinephrine. Guanabenz did not elicit secretory responses in either the presence or absence of idazoxan. These results argue that two components determine the magnitude of the sialagogic response induced by agonists with mixed alpha 1/alpha 2 activity: (a) an alpha 1-mediated secretory effect and (2) an alpha 2-mediated inhibitory effect, both being localized at postsynaptic level.

Adrenergic alpha-Agonists↗
PubMed1986

Sympathetic and parasympathetic nerves regulate postsynaptic alpha-2 adrenoceptor in salivary glands.

The effects of sympathetic denervation or parasympathetic decentralization on the inhibitory effects of postsynaptic alpha-2 adrenoceptors were studied in the submaxillary and the sublingual gland of the rat. Chronic sympathetic denervation enhanced by a factor of 10 the potency of clonidine to inhibit the secretory responses of the submaxillary gland to either norepinephrine or methacholine. In denervated glands, clonidine (1 microgram/kg), reduced markedly the response to norepinephrine, but potentiated this response in control glands. Blockade of postsynaptic alpha-2 adrenoceptors with idazoxan (3 micrograms/kg) enhanced the secretory responses of denervated glands to norepinephrine. Parasympathetic decentralization also potentiated the inhibitory effects of the alpha-2 agonists. In the submaxillary gland the potency of guanabenz to decrease the secretory response to methacholine was increased by a factor of 30. Supersensitivity to the inhibitory effects of clonidine was also observed in parasympathetically decentralized sublingual glands. Parasympathetic decentralization increased the maximum binding site of [3H]clonidine binding by about 50% in both the submaxillary and sublingual glands. No changes in KD were detected. This surgical procedure also increased the maximum binding site of [3H]prazosin binding in submaxillary glands. The present findings show clearly that interruption of either branch of the autonomic nervous system induces supersensitivity of the inhibitory response mediated through postsynaptic alpha-2 adrenoceptors. The enhanced inhibitory activity could mask alpha-1 adrenoceptor supersensitivity after postganglionic sympathetic denervation.

Animals↗
PubMed1985

Effects of guanabenz and guanfacine on postsynaptic alpha 2-adrenoceptors in the rat submaxillary and parotid glands.

The effects of two alpha 2-agonists (guanfacine and guanabenz) on both the submaxillary and parotid gland of the rat were studied. Whereas guanfacine in doses ranging between 1,000 and 30,000 micrograms/kg i.v. produced an immediate and persistent secretion of saliva from the submaxillary gland, guanabenz in doses as high as 40,000 micrograms/kg did not induce measurable secretion either from the parotid or the submaxillary gland. Secretion elicited by guanfacine was not modified by yohimbine (300 micrograms/kg) but was abolished by prazosin (100 micrograms/kg). In both glands, low doses of either guanabenz (10 micrograms/kg) or guanfacine (100 micrograms/kg) markedly inhibited the secretory responses induced by noradrenaline, methacholine and substance P, but not that induced by isoprenaline. The inhibition caused by the alpha 2-agonists was greater for noradrenaline than for either methacholine or substance P. Blockade of alpha 2-adrenoceptors with yohimbine (300 micrograms/kg) did not modify the response to noradrenaline, methacholine or substance P in either gland. However, the same dose of yohimbine injected 5 min before the alpha 2-agonists prevented the inhibitory effects of guanfacine and guanabenz on the response induced by either one of the three sialagogic agents. Guanabenz (10 micrograms/kg) did not modify the increase in mean blood pressure observed after the different doses of noradrenaline employed to induce salivary secretion. Guanabenz (10 micrograms/kg) and guanfacine (100 micrograms/kg) did not change the time course of the secretion elicited by either noradrenaline, methacholine or substance P, since the degree of inhibition was of similar magnitude at all the periods of time analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1984

Clonidine inhibits salivary secretion by activation of postsynaptic alpha 2-receptors.

The effects of clonidine on the submaxillary gland of the rat were studied. Doses ranging between 100 to 3.000 micrograms/kg produced a sustained secretory response which was blocked by 0.1 mg/kg of prazosin but not by 1 mg/kg of yohimbine. Clonidine 10 micrograms/kg markedly inhibited the salivation induced by noradrenaline, methacholine and substance P but not that induced by isoproterenol. The inhibition caused by the alpha 2-agonist was greater for noradrenaline than for either methacholine or substance P. Blockade of alpha 2 adrenoceptors with yohimbine (0.3 - 1 mg/kg) prevented the inhibition by clonidine of noradrenaline, methacholine and substance P induced salivation. On the other hand, prazosin 0.1 mg/kg did not modify the inhibition by clonidine of methacholine induced secretion. The results obtained indicate that clonidine exerts a dual effect on salivary secretion: at high doses it elicits salivation through activation of alpha 1-adrenoceptors; at the dose of 10 micrograms/kg clonidine activates alpha 2-adrenoceptors which inhibit the secretory response evoked through either muscarine, substance P and alpha 1-adrenoceptor agonists.

Animals↗
PubMed1984

Alpha-1 adrenoceptors mediate secretory responses to norepinephrine in innervated and denervated rat submaxillary glands.

The alpha adrenoceptor that mediates the secretory responses to norepinephrine in submaxillary glands was characterized. All three alpha antagonists employed produced in innervated glands parallel displacements of the dose-response curves to norepinephrine, prazosin being 30 and 100 times more potent than phentolamine and yohimbine, respectively. Chronic sympathetic denervation produced supersensitivity to norepinephrine. Under these conditions prazosin also was more potent than yohimbine but the shifts of the dose-response curves to norepinephrine were nonparallel. Potentiation of norepinephrine by cocaine did not modify the effects of prazosin in innervated glands. The nonparallel displacements observed in denervated glands were related to the development of postjunctional supersensitivity of the beta adrenoceptor-mediated responses because after administration of propranolol the displacements produced by prazosin were parallel. Responses to methoxamine were not potentiated by denervation and were competitively antagonized by prazosin in both innervated and denervated glands. Specific [3H]clonidine binding to membranes of submaxillary glands showed at least two independent sites with a KD1 of 0.37 nM and a KD2 of 65 nM. The number of sites of each component was doubled after chronic sympathetic denervation. Binding of [3H]prazosin (KD, 0.43 nM; maximum binding sites, 78.5 fmol/mg of protein) was not affected by denervation. The present findings show that sialagogue responses to sympathomimetic agents are mediated by alpha-1 adrenoceptor activation in both innervated and denervated submaxillary glands. Chronic sympathetic denervation does not produce postjunctional supersensitivity of the alpha-1-mediated responses and the supersensitivity of the beta-mediated responses interferes with determinations of dose-response curves to the sympathetic neurotransmitter.

Animals↗
PubMed1980

Effect of chronic alcohol feeding on adrenergic and cholinergic neurotransmission mechanism.

Experimental data is presented indicating that chronic alcohol consumption in rats has a direct CNS effect resulting in increased activity of the autonomic nervous outflow. Changes in neurohormonal transmitters have been demonstrated in four organs: salivary glands, spleen, adrenals and heart. These changes may account for the alterations in end organ sensitivity and secretory patterns which occur in alcoholic animals and man. They may, moreover, represent an initial pathogenetic mechanism whereby alcohol induces its various clinical syndromes.

Acetylcholinesterase↗
PubMed1979

Effects of sympathectomy on the in vivo alpha and beta-responses of the parotid gland.

Salivary secretion in response to noradrenaline and isoprenaline was measured in innervated and chronically sympathectomized parotid glands of the rat. In innervated glands, the responses to isoprenaline lasted longer than those to noradrenaline. Chronic sympathetic denervation enhanced the responses to both noradrenaline and isoprenaline. The magnitude of the supersensitivity to isoprenaline was related to the dose and the time at which the responses were analyzed. Supersensitivity was greater for the initial than for the total secretion elicited by isoprenaline. Propranolol (1 mg/kg) and phentolamine (5 mg/kg) were used in order to determine the relative participation of alpha and beta-adrenoceptors in the enhanced responses to isoprenaline. The results suggest that postjunctional supersensitivity for the secretory responses of this organ to isoprenaline is mainly mediated through beta-adrenoceptors of the secretory cells and alpha-adrenoceptors of the myoepithelial cells.

Animals↗