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Biomedical subjects

F J Stefano

Publications and source records attributed to F J Stefano.

At least 37 records · Page 2Linked to original sources
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

Saturation of monoamine oxidase by intraneuronal noradrenaline accumulation.

After pretreatment of the rats with reserpine and pargyline (to inhibit vesicular uptake and MAO), after an additional in vitro treatment with pargyline, and in the presence of U-0521 (to inhibit COMT), the adrenergic nerve endings of vasa deferentia were loaded with 3H-(-)-noradrenaline by exposure to various concentrations of this amine. Subsequently, tissues were washed out with amine-free solution, and the neuronal efflux of tritium was analysed. During 180 min of wash-out the apparent rate constant for the efflux of tritium decreased with increasing tritium content of the tissue. Prolongation of the wash-out period to 305 min revealed that efflux curves for tritium from heavily loaded tissues became steeper after the 180th min of wash-out. This phenomenon is indicative of saturation (followed by desaturation) of a process that limits the efflux of tritium from heavily loaded tissues. Analysis of the radioactivity of the efflux revealed a characteristic efflux curve for DOPEG: the formation of DOPEG appears to be saturated when the 3H-(-)-noradrenaline content of the tissue is high, in order to become desaturated during prolonged wash-out. These results cannot distinguish between MAO and alcohol dehydrogenase as the saturable enzyme. The formation of the mainly deaminated metabolites (during 60 min of wash-out) was determined in lightly and in heavily loaded tissues. The ratio "formation of metabolites/3H-(-)-noradrenaline content" was lower in heavily than in lightly loaded tissues; the relative decline in DOPEG formation was not accompanied by a compensatory increase in the formation of DOMA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Amphetamine-clonidine interaction on neurotransmission in the vas deferens of the rat.

The interaction between amphetamine and clonidine on neurotransmission in the rat vas deferens was studied. In the whole vas deferens, clonidine 0.037 mumol/l displaced to the right the frequency-response curve evoked by either hypogastric or field stimulation. The frequency of stimulation that produced 50% of the maximal response (EF 50) was: control 4.0 Hz, clonidine 18.3 Hz (P less than 0.001 n = 4), for hypogastric nerve stimulation; and 2.1 Hz in controls and 17.1 Hz in clonidine-treated preparations, for field stimulation (P less than 0.001 n = 5). Preincubation with 5.4 mumol/l amphetamine antagonized the effect of clonidine (EF 50 amphetamine alone 6.2 Hz, amphetamine + clonidine 7.3 Hz; P greater than 0.5). After 12 min of incubation with clonidine 0.037 mumol/l the responses to 6.4 Hz (3 s, 0.5 ms) were decreased by 77 +/- 2.2%. Both yohimbine and amphetamine, in a concentration-dependent manner, attenuated the inhibition. Washout of clonidine produced a slow recovery of the responses. Inhibition of the motor response to nerve stimulation (6.4 Hz, 3 s) by 30 mumol/l 2',3'-cAMP was increased by 10 mumol/l dipyridamole and impaired by 100 mumol/l theophylline. Amphetamine, in a concentration that markedly reduced clonidine inhibition of neurotransmission failed to antagonize 2',3'-cAMP. In the bisected vas deferens clonidine inhibited the peak motor response to short trains of field stimuli in the prostatic portion ("non-adrenergic") and the sustained response in the epididymal portion ("adrenergic"). Yohimbine potentiated both types of responses and fully prevented the effect of clonidine. In the prostatic portion amphetamine slightly inhibited the peak motor response and attenuated the inhibitory effect of clonidine in both portions of the vas.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
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↗
PubMed1982

Degeneration activity of the pineal gland after sympathetic denervation.

After removal of the superior cervical ganglia the pineal gland of the rat showed a period of transient increase in activity of serotonin-N-acetyltransferase. This degeneration activity was preceded by a decline of the levels of endogenous noradrenaline and an impairment of the 3H-metaraminol uptake. Twenty-seven hours after sympathetic denervation the levels of the endogenous neurotransmitter were almost completely depleted, while either 24 h or 21 days after denervation total uptake of the tritiated amine decreased to only about 50% of the control values. Previous chronic sympathetic decentralization elicited in the pineal gland post-junctional supersensitivity, as judged by the enhanced degeneration activity observed in decentralized glands after sympathetic denervation. The present findings confirm that, in endocrine glands and similarly to other autonomically innervated organs, acute denervation induces degeneration activity.

Animals↗
PubMed1982

Electron microscopic evidence that bretylium and pargyline delay adrenergic nerve degeneration after sympathectomy of the pineal gland.

Seventeen and twenty four hours after sympathetic denervation, noradrenaline stores of the rat pineal gland were depleted to 50% and 10% of controls, respectively. Electron microscopic studies showed the coexistence of normal and altered nerve endings 17 h after denervation, while 24 h after denervation, only degenerated nerve terminals were observed. Treatment with pargyline (512 mumoles/kg) or bretylium (24 mumoles/kg) significantly delayed the loss of noradrenaline from denervated glands. In pargyline treated rats, 17 h after denervation, noradrenaline stores were 90% of control glands. After bretylium, values obtained 24 h after denervation, declined to 36% of innervated glands. Persistence of neurotransmitter coincided with the presence of normal nerve endings as observed electron microscopically. It is concluded that both, pargyline and bretylium, prolonged the survival of nerve endings severed from the cell body.

Adrenergic Fibers↗
PubMed1982

Delay by drugs of adrenergic nerve degeneration after proximal or distal sympathectomy of the submaxillary gland.

1. Degeneration of nerve terminals of the submaxillary gland of the rat proceeds at a faster rate after crushing adrenergic nerves close to the gland than after ganglionectomy. 2. Bretylium, pargyline, nialamide and clorgyline delayed degeneration to the same extent after either type of denervation. 3. Chlorpromazine and pentobarbitone also delayed adrenergic degeneration, effect related to the hypothermia induced by these drugs. 4. Colchicine applied on the nerve trunk innervating the right gland delayed not only degeneration of the ipsilateral nerve terminals but the contralateral gland as well. 5. From the data obtained it seems probable that the drugs tested delay adrenergic nerve degeneration at the levels of nerve terminals. This effect is not related to lysosomal stabilization.

Acid Phosphatase↗
PubMed1982

Cardiovascular effects of 2-Br-alpha-ergocriptine in urethane anesthetized rats.

Experiments were designed to study the cardiovascular effects of Bromocriptine (2-Br-alpha-ergocriptine) in the normotensive anesthetized rats. The intravenous administration of bromocriptine (20 micrograms/kg and 200 micrograms/kg) produced a long-lasting and not dose-dependent fall in the mean blood pressure and heart rate. The pressor response to phenylephrine, an alpha adrenergic agonist, was antagonized by bromocriptine in a dose-dependent manner. At a dose of 20 micrograms/kg bromocriptine behaved as a competitive antagonist, whereas at the dose of 200 micrograms/kg produced an insurmountable blockade of the response to phenylephrine. Previous administration of phentolamine (5 mg/kg) prevented the insurmountable blockade of alpha adrenoceptors by bromocriptine. This observation suggests that both drugs compete for the same receptor. It is concluded that blockade of peripheral alpha-adrenoceptors may contribute to cardiovascular effects of bromocriptine.

Anesthesia↗
PubMed1981

Effects of alpha-bromoergocryptine on pituitary hormone secretion in children.

The effect of bromoergocryptine (BE) on human GH (hGH), PRL, LH, FSH, TSH, and blood sugar levels was evaluated in a series of 22 normal children. Blood samples were collected in basal conditions and after 30, 60, 90, 120, 150, and 180 min of BE administration (1.25 or 0.62 mg/os). The drug induced a marked and sustained increase in hGH secretion when basal serum levels of the hormone were lower than 10.0 ng/ml (n = 15). When basal hGH serum levels were higher (n = 7), BE provoked either a later increase of serum hGH in most children (n = 5) or a persistent decrease in hGH (n = 2). On the other hand, BE markedly inhibited PRL secretion without modifying LH, FSH, or TSH. The data obtained suggest that BE can be used as a useful tool for the assessment of hGH secretion in children.

Adolescent↗
PubMed1981

In vitro release of 3H-noradrenaline by amphetamine from the superior cervical ganglion of the cat.

The release and metabolism of 3H-noradrenaline (3H-NA) produced by d-amphetamine was studied in the superior cervical ganglion of the cat (cell bodies) and in the nictitating membrane (nerve endings). Exposure of the nictitating membrane to 10 microM d-amphetamine, resulted in the release of 5.1% of the total radioactivity. This was mainly collected as 3H-normetanephrine (3H-NMN) and as 3H-NA; 3H-3,4-dihydroxyphenylglycol (3H-DOPEG) did not contribute to the drug-induced outflow of radioactivity. In contrast, exposure of ganglionic cell bodies to 10 microM d-amphetamine for 10 min released only 1.74% of the total tissue radioactivity and 3H-DOPEG represented the most important fraction of the released radioactivity. When ganglia were exposed to 30 microM d-amphetamine, the radioactivity released was 5.2%; the proportion of 3H-NA and 3H-NMN increased and 3H-DOPEG was reduced. These results show that: a) d-amphetamine releases 3H-NA from prelabeled cell bodies and nerve endings; b) the potency of d-amphetamine was higher in nerve terminals than in cell bodies, and c) at low concentrations of d-amphetamine, the metabolism of the released neurotransmitter differed between both parts of the adrenergic neuron.

Animals↗
PubMed1980

Delay by bretylium of adrenergic nerve degeneration after sympathectomy of the submaxillary gland.

Administration of 24 mumol/kg of bretylium 10 h after ganglionectomy delayed the loss of endogenous norepinephrine and the impairment of neuronal uptake of 3H-metaraminol (3H-MA) that follow sympathetic denervation. This delay was evident 16 and 20 h after denervation. Twenty four h after ganglionectomy, when NE stores and uptake of 3H-MA were reduced to their lowest values in untreated rats, in bretylium-treated ones these values were approximately 40% of those in normal glands. The onset of degeneration secretion in treated rats was delayed by about 9 h. The development of prejunctional supersensitivity was also delayed. The subcellular distribution of NE in normal and 16 h denervated glands showed that denervation reduced the neurotransmitter to the same extent in the 3 fractions: coarse, supernatant and microsomal. Treatment with bretylium and pargyline prevented the loss of NE from the microsomal fraction. Previous administration of pargyline antagonized the protection of 3H-MA uptake seen in 28 h denervated rats treated with bretylium. However, this drug combination induced a greater retention of endogenous NE 24 h after denervation. Bretylium inhibited intraneuronal MAO by 40%. It is concluded that bretylium treatment can delay the degeneration of adrenergic nerve terminals separated from the cell bodies by a pharmacological effect probably not related to MAO inhibition or to its neurone blocking action.

Animals↗
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↗
PubMed1979

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

Amylase and K+ resease were measured in slices obtained from innervated and sympathetically denervated rat parotid glands. Amylase release induced by noradrenaline was found to be increased after chronic denervation. The postjunctional component of supersensitivity to noradrenaline was evidenced by an increase in the maximal response to this agonist. The maximal response of denervated glands was blocked by propranolol 10(-5) M. On the other hand, chronic denervation did not modify the alpha-adrenoceptor-mediated response, K+ release, either in the presence or in the absence of ouabain. It is concluded that, after sympathetic denervation, postjunctional supersensitivity develops for the beta-adrenoceptor-mediated but not for the alpha-adrenoceptors-mediated effects of noradrenaline.

Amylases↗