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B G Livett

Publications and source records attributed to B G Livett.

At least 37 records · Page 2Linked to original sources
PubMed1991

Substance P-containing sensory neurons in the rat dorsal root ganglia innervate the adrenal medulla.

The adrenal medulla is innervated by both cholinergic and substance P (SP)-containing fibres via the splanchnic nerve. SP has been shown to modulate catecholamine (CA) secretion in isolated chromaffin cells and in the perfused rat adrenal gland, however, the origin of SP-containing fibres is not known. In the present study, we have combined the techniques of SP immunohistochemistry and retrograde tracing with Fast blue injected into the left adrenal medulla of the rat in order to study whether SP-containing sensory neurons in the dorsal root ganglia innervate the adrenal medulla. The results showed that there were on average 281 +/- 31 SP-like immunoreactive cells in each left dorsal root ganglion, T3-T13 (range, 234 +/- 19 in T4 to 372 +/- 43 in T13, n = 8). The average total number of Fast blue-labelled cells (T3-T13) in 8 experiments was 172 +/- 26, distributed normally about a peak at T8 (33.8 +/- 6.3 cells) and T9 (33.3 +/- 6.8 cells) with the least at T3 (1.5 +/- 0.8) and T13 (5.2 +/- 2.0). No Fast blue-labelled cells were found in the right DRG. In the left DRG, the average number of cells exhibiting both SP and Fast blue labelled cells were distributed from T7 to T9. These results demonstrate that SP-containing sensory neurons in the dorsal root ganglia provide an ipsilateral innervation of the adrenal medulla in rats.

Adrenal Medulla↗
PubMed1991

Coordinate and differential regulation of proenkephalin A and PNMT mRNA expression in cultured bovine adrenal chromaffin cells: responses to secretory stimuli.

The expression of proenkephalin A (ProEnk A) mRNA and phenylethanolamine N-methyltransferase (PNMT) mRNA in response to nicotine and to a number of secretagogues was examined in cultured bovine adrenal chromaffin cells. Prolonged incubation with nicotine (10 microM) resulted in a 2-fold increase in ProEnk A mRNA but had no significant effect on the level of PNMT mRNA. Similarly, prolonged stimulation with high K+ (56 mM) induced a time-dependent elevation in the level of ProEnk A mRNA reaching 4-fold basal level after 24 h incubation. By contrast, the level of PNMT mRNA was not changed by treatment with high K+. The increase in the level of ProEnk A mRNA by high K+ was abolished by the presence of 10 microM D600, a calcium channel blocker. Unlike the effects of high K+, treatment of the cells with the sodium channel activator veratridine significantly elevated the levels of both ProEnk A and PNMT mRNA. This increase in ProEnk A and PNMT mRNA levels was however less affected by D600. Stimulation of the cells with Ba2+ (1.1 mM) also stimulated the levels of ProEnk A and PNMT mRNA and this action required the presence of extracellular Ca2+. This was in contrast to the effect of Ba2+ in stimulating catecholamine secretion, which was inhibited by Ca2+ and enhanced in Ca2(+)-free buffer. The results of the present study indicate that membrane depolarization and entry of extracellular Ca2+ play an important role on the regulation of ProEnk A and PNMT mRNAs, in addition to their well-known actions on hormone secretion. Furthermore, these results suggest that the expression of ProEnk A mRNA and PNMT mRNA are under independent regulation in response to secretory stimulation.

Adrenal Medulla↗
PubMed1991

Coordinate and differential regulation of proenkephalin A and PNMT mRNA expression in cultured bovine adrenal chromaffin cells: responses to cAMP elevation and phorbol esters.

The expression of proenkephalin A (ProEnk A) mRNA and phenylethanolamine N-methyltransferase (PNMT) mRNA in response to cAMP analogues, forskolin and phorbol esters was examined in cultures of bovine adrenal chromaffin cells. Exposure of chromaffin cells to 1 mM dibutyryl cAMP for 24 h increased significantly the levels of ProEnk A mRNA, with no significant effect on the levels of PNMT mRNA. Cells exposed to the tumor promoting phorbol esters (phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate or 4-beta-phorbol 12,13-didecanoate) for 12 h differentially activated PNMT mRNA and ProEnk A mRNA expression. The levels of PNMT mRNA were dramatically elevated in response to low concentrations (10(-9) to 10(-8)M) of these phorbol esters, but these increases were diminished at higher concentrations (10(-7) to 10(-6) M) of the phorbol esters. These responses were synergistically potentiated by dexamethasone (1 microM), a synthetic glucocorticoid. None of these effects was seen with the biologically inactive phorbol ester, 4-alpha-phorbol 12,13-didecanoate. By contrast, the expression of ProEnk A mRNA was activated by the tumor promoting phorbol esters in a concentration-dependent manner. The results of this study demonstrate a differential stimulatory effect of second messenger mechanisms in the control of PNMT and ProEnK A mRNA expression and provide further evidence for an independent control for the enkephalin and adrenaline synthesis in these cells.

Adrenal Medulla↗
PubMed1991

Substance P modulates the time course of nicotinic but not muscarinic catecholamine secretion from perfused adrenal glands of rat.

1. Substance P (SP) and acetylcholine (ACh) are contained within the splanchnic nerve terminals in the adrenal gland and can be released in response to stress. In the rat, the release of aCh brings about secretion of catecholamines (CA) by acting on nicotinic and muscarinic receptors on the adrenal chromaffin cells. 2. In the present study, we have used a rat isolated adrenal gland preparation to investigate the effects of SP, perfused at different concentrations, on CA secretion evoked by 10(-5) M nicotine and 10(-4) M muscarine. 3. In the first 10 min stimulation period (S1), in the absence of SP, nicotine (10(-5) M) evoked substantial and equal secretion of noradrenaline (NA) and adrenaline (Ad). In a second 10 min stimulation period (S2), carried out 18 min after S1, the nicotinic response was desensitized. In contrast, the muscarinic response, which preferentially evoked Ad secretion in S1 (Ad/NA: 8.7/1), was well maintained in S2. 4. SP present in S1 had no effect on desensitization of the subsequent nicotinic response in S2. 5. At low concentrations (10(-7)-10(-10) M), SP changed the time course of nicotine-induced CA secretion during S1 by enhancing CA secretion in the first 4 min and inhibiting CA secretion thereafter. The maximal effect occurred at 10(-9) M SP. 6. At a higher concentration (10(-5) M), SP inhibited total nicotinic CA secretion throughout S1 and produced a biphasic secretion of CA (depressed in the presence of SP and enhanced after wash out of SP). Pre-exposure of adrenal glands to SP (10-' to 10- M) for 10min produced marked inhibition of the nicotine-induced CA secretion. 7. In contrast to the effect of SP on the nicotinic response, SP from 10- to 10-SM had no effect on muscarinic CA secretion. 8. This difference in sensitivity of the nicotinic and muscarinic responses to SP points to a diversity of mechanisms available for control of adrenal catecholamine secretion. In addition to the ability of SP to increase or decrease the total amount of adrenal CA secretion, dependent on the concentration of SP, the present study shows that SP can change the time-course of nicotinic CA secretion. These results with the rat adrenal gland perfused in vitro suggests both a quantitative and temporal role for SP as a novel modulator of adrenal CA secretion.

Adrenal Glands↗
PubMed1991

Capsaicin-sensitive sensory neurons are involved in the plasma catecholamine response of rats to selective stressors.

1. The effect of capsaicin pre-treatment on adrenal catecholamine (CA) secretion in response to stress is controversial. In earlier experiments performed under pentobarbitone anaesthesia, the release of CA in response to stress was complicated by the effects of the barbiturate anaesthesia. 2. In the present study we have used conscious freely moving rats with indwelling cannulae to study the effect of neonatal capsaicin pre-treatment on the plasma CA response to different types of stressors (swimming stress, hypovolaemic stress, immobilization stress and cold stress). 3. After swimming for 20 min, plasma noradrenaline (NA) levels increased by 8-fold and adrenaline by 2-fold in control rats. The increase in plasma NA levels in the capsaicin group was attenuated at 10 min of swimming compared with the vehicle group (P < 0.05). 4. With hypovolaemic stress, there were no differences in plasma CA levels, blood pressure and heart rate between the capsaicin group and the vehicle group. There were also no differences in plasma CA levels after immobilization stress between the two groups. 5. With cold stress, plasma NA levels increased 5-fold and adrenaline levels by 3-fold over basal at 45 min in the vehicle pre-treated rats. This increase was not observed in the capsaicin group. 6. Immunoreactive substance P was depleted by only 68% in the splanchnic nerve following capsaicin pre-treatment. If the remaining 32% was biologically active substance P then it could account for the maintenance of the response to hypovolaemic and immobilization stress. However, it might be possible that the responses to hypovolaemic and immobilization stresses could be attenuated if a more complete depletion were achieved. 7. These results in conscious rats indicate that capsaicin-sensitive sensory neurons are required for plasma CA response to selective stressors. They are required for CA output in response to cold stress and to the early phase of swimming stress, but not to hypovolaemic stress and immobilization stress.

Animals↗
PubMed1990

Role of capsaicin-sensitive neurons in catecholamine secretion from rat adrenal glands.

Sensory fibres innervate the adrenal medulla but their function is not known. In the present study, we have used the sensory neurotoxin capsaicin to evaluate the effect of capsaicin sensitive sensory fibres on catecholamine (CA) secretion from isolated perfused rat adrenal glands. CA secretion in response to 1 and 10 min electrical field stimulation of adrenal nerve terminals was significantly attenuated in the adrenal glands of adult rats pretreated as neonates with capsaicin and was frequency dependent, being more pronounced at the higher frequencies of stimulation (5 to 30 Hz) than at the low (0.3, 1 Hz) frequencies. Perfusion of control rat adrenal glands with capsaicin did not evoke CA secretion, but did increase CA secretion in response to perfusion with nicotine. Perfusion with capsaicin for 30 min (but not for 4 min) reduced the CA secretory response to subsequent nerve stimulation. The results suggest that capsaicin sensitive sensory neurons innervating the adrenal medulla are involved in the regulation of adrenal CA secretion evoked by electrical stimulation of adrenal nerve terminals.

Adrenal Glands↗
PubMed1990

Hypovolaemia can potentiate hypoglycaemic stress-induced adrenaline release in the anaesthetized rat.

The interaction between hypoglycaemic stress and hypovolaemic stress in promoting adrenaline secretion from the adrenal medulla has been studied in anaesthetised and conscious rats. In anaesthetized rats, insulin (1 IU/kg, i.v.) markedly increased plasma adrenaline concentrations whereas blood sampling alone did not. The hypoglycaemic response to insulin was greatly reduced if donor blood was used instead of saline to replace the withdrawn blood. The hypoglycaemic response was abolished by captopril or saralasin. The results suggest that adrenaline secretion in response to hypoglycaemic stress in anaesthetized rats is potentiated by hypovolaemic activation of the renin-angiotensin system. In contrast, in fully conscious rats, the response to hypoglycaemia was not abolished by captopril, indicating that in the absence of barbiturate anaesthesia, the hypoglycaemic release of catecholamines is not potentiated by the renin-angiotensin system.

Adrenal Medulla↗
PubMed1990

A novel substance P binding site in bovine adrenal medulla.

Radioligand binding techniques were used to characterize the substance P (SP) binding site on membranes prepared from bovine adrenal medullae. 125I-labelled Bolton-Hunter substance P (BHSP), which recognises the C-terminally directed, SP-preferring NK1 receptor, showed no specific binding. In contrast, binding of [3H]SP was saturable (at 6 nM) and reversible, with an equilibrium dissociation constant (Kd) 1.46 +/- 0.73 nM, Bmax 0.73 +/- 0.06 pmol/g wet weight and Hill coefficient 0.98 +/- 0.01. Specific binding of [3H]SP was displaced by SP greater than neurokinin A (NKA) greater than SP(3-11) approximately SP(1-9) greater than SP(1-7) approximately SP(1-4) approximately SP(1-6), with neurokinin B (NKB) and SP(1-3) very weak competitors and SP(5-11), SP(7-11) and SP(9-11) causing negligible inhibition (up to 10 microM). This potency order is quite distinct from that seen with binding to an NK1 site, a conclusion confirmed by the lack of BHSP binding. It appears that Lys3 and/or Pro4 are critical for binding, suggesting an anionic binding site. These data suggest the existence of an unusual binding site which may represent a novel SP receptor. This site appears to require the entire sequence of the SP molecule for full recognition.

Adrenal Medulla↗
PubMed1990

Peptide regulation of adrenal medullary function.

The discovery of peptides in the splanchnic nerve and adrenal gland, and their co-existence with conventional neurotransmitters raises questions about their possible functional roles in catecholamine (CA) secretion and gene transcription in the adrenal gland. Short-term, stress-induced CA secretion is regulated biphasically by substance P (SP) which inhibits acetylcholine (ACh) action at SP greater than 10(-6) M and facilitates CA secretion in response to metabolic and physical stressors, ACh or electrical stimulation at SP less than 10(-6) M. Long-term, gene transcription of phenylethanolamine-N-methyltransferase (PNMT) is exerted by glucocorticoids, and gene transcription of Proenkephalin-A by agents such as histamine, angiotensin II and VIP that increase cyclic AMP (cAMP). The final products of these two genes, adrenaline and Met-enkephalin and congeners, are co-stored in chromaffin granules of adrenaline cells but gene expression of these products is clearly under differential control.

Adrenal Medulla↗
PubMed1990

Receptor stimulated formation of inositol phosphates in cultures of bovine adrenal medullary cells: the effects of bradykinin, bombesin and neurotensin.

The ability of a number of drugs and neuropeptides to stimulate phosphoinositide metabolism in cultured bovine adrenal medullary cells has been assessed. Low concentrations (10 nM) of angiotensin II, bradykinin, histamine, arginine-vasopressin, and bombesin, and high (10 microM) concentrations of oxytocin, prostaglandins E1, and E2, beta-endorphin, and neurotensin stimulated significant accumulation of [3H]inositol phosphates in adrenal medullary cells preloaded with [3H)]inositol. Bradykinin stimulated a significant response at concentration as low as 10pM, with an EC50 of approximately 0.5 nM. The response was markedly inhibited by the bradykinin B2 antagonist [Thi5,8,D-Phe7] bradykinin but not the B1 antagonist [Des-Arg9,Leu8] bradykinin. Higher concentrations of bombesin and neurotensin were required to elicit a response (10 nM and 10 microM respectively). The bombesin response was sensitive to inhibition by the bombesin antagonist [D-Arg1,D-Pro2,D-Trp7,9Leu11]-substance P. In contrast, the neurotensin response was not reduced by the NT1 antagonist [D-Trp11]-neurotensin. These results indicate there are a number of agents that can stimulate phosphatidylinositide hydrolysis in the adrenal medullary cells by acting on different classes of receptors. Such a range of diverse agonists that stimulate inositol phosphate formation will facilitate further analysis of the phosphatidylinositide breakdown in chromaffin cell function.

Adrenal Medulla↗
PubMed1990

Angiotensin II stimulates the expression of proenkephalin A mRNA in cultured bovine adrenal chromaffin cells.

The effects of angiotensin II on the expression of proenkephalin A (ProEnk A) mRNA and enkephalin release were examined in cultured bovine adrenal chromaffin cells. Exposure of chromaffin cells for 24h to 10 nM angiotensin II produced a more than 2-fold increase in cellular ProEnk A mRNA levels with a concomitant elevation in the levels of high molecular weight Met5-enkephalin-Arg6-Gly7-Leu8-like immunoreactivity in the culture medium. These stimulatory effects of angiotensin II on enkephalin release and mRNA expression were fully antagonized by the angiotensin II antagonist [Sar1, Ala8]-angiotensin II. The angiotensin II-induced increase in ProEnk A mRNA levels was also abolished by the RNA synthesis inhibitor actinomycin D. These results indicate that specific angiotensin II receptor activation is responsible for stimulating transcription of ProEnk A mRNA and enkephalin. Angiotensin II may therefore be involved in the long-term regulation of ProEnk A gene expression in the adrenal medulla.

Adrenal Medulla↗
PubMed1990

Substance P has biphasic effects on catecholamine secretion evoked by electrical stimulation of perfused rat adrenal glands in vitro.

The adrenal medulla is innervated by the splanchnic nerve which contains substance P-immunoreactive fibres originating in the dorsal root ganglia but whose function in the adrenal medulla is not known. In the present study, we have examined the effect of exogenous substance P on catecholamine secretion and [3H]-choline overflow evoked by field stimulation of the perfused rat adrenal gland. Substance P had biphasic effects on catecholamine secretion evoked by field stimulation: at the lower concentrations (10(-7)-3 x 10(-6) M), substance P facilitated catecholamine secretion whereas at higher concentrations (3 x 10(-5) M), substance P inhibited catecholamine secretion. The effects of substance P were long-lasting: substance P at all concentrations present during the second of three 6-min stimulations increased catecholamine secretion during the third stimulation. The enhancement of catecholamine secretion by substance P during field stimulation was not blocked by atropine but was substantially blocked by hexamethonium plus atropine. Substance P at all concentrations inhibited the evoked [3H]-choline overflow with a maximal inhibition of 60% (at 10(-6) M). In the absence of stimulation, substance P (10(-7)-3 x 10(-5) M) had no effect on the basal catecholamine secretion or basal [3H]-choline overflow. These results indicate that substance P has modulatory effects on adrenal catecholamine secretion and [3H]-choline overflow evoked by electrical stimulation. Presynaptically, substance P inhibits transmitter overflow from cholinergic nerve terminals and post-synaptically substance P has biphasic effects on catecholamine secretion dependent on the substance P concentration. These results suggest a functional role for substance P-containing fibres innervating the adrenal medulla.

Adrenal Glands↗
PubMed1990

Effect of capsaicin-sensitive sensory nerves on plasma glucose and catecholamine levels during 2-deoxyglucose-induced stress in conscious rats.

1. Sensory fibres innervate the adrenal medulla but their function is not known. In this paper we have studied the effect of capsaicin-sensitive sensory fibres on the adrenal catecholamine (CA) response and blood glucose response to 2-deoxyglucose (2-DG)-induced glucopenic stress in conscious rats. 2. 2-DG at 500 mg kg-1 (i.v.) induced a 2.5 fold increase in plasma glucose levels, a 3.5 fold increase in inferior vena caval (i.v.c.) plasma noradrenaline (NA) levels and a 7 fold increase in i.v.c. plasma adrenaline (Ad) levels over 60 min. The hyperglyaemia in response to 2-DG was attenuated by pentolinium and by left splanchnicotomy plus right adrenalectomy. These procedures also caused a complete inhibition of the increase in plasma CA. 3. The hyperglycaemia in response to 2-DG was attenuated by pretreatment of rats with capsaicin as neonates, suggesting that capsaicin-sensitive sensory fibres are required for regulation of plasma glucose in response to glucopenic stress. 4. The increase in i.v.c. plasma CA levels in response to 2-DG during the early phase of glucopenia (first 30 min) in the conscious rats pretreated with capsaicin was the same as in the rats pretreated with vehicle alone. During the later phase of glucopenia (after 45 min), the increase in plasma CA levels in rats pretreated with capsaicin was higher than in the rats pretreated with vehicle alone. 5. In vehicle-pretreated rats and capsaicin-pretreated rats the tissue NA and Ad levels in the adrenal medulla after 8 h of stress were depleted to the same extent. However, tissue CA levels in the capsaicin group recovered faster over 24 h than in the vehicle group. 6. These results indicate that capsaicin-sensitive sensory fibres are not required to maintain adrenal CA secretion during glucopenic stress in the conscious rat but are required for maintenance of blood glucose levels.

Adrenal Medulla↗
PubMed1990

Substance P increases catecholamine secretion from perfused rat adrenal glands evoked by prolonged field stimulation.

1. We have studied the effect of substance P (SP) on catecholamine (CA) secretion evoked by prolonged field stimulation from the perfused rat adrenal gland in vitro. 2. Previous studies show that SP has an inhibitory effect on the nicotinic response in a number of different tissue preparations. In the present study, we found that SP at concentrations from 10(-7) to 10(-6) M markedly increased CA secretion evoked by prolonged high-frequency field stimulation but not that evoked by low-frequency field stimulation. 3. In the absence of field stimulation SP by itself had no direct effect on CA secretion. This indicates that SP acts as a neuromodulator rather than a neurotransmitter to increase CA secretion from the adrenal medulla. 4. The nicotinic receptors were still functional following a period of prolonged field stimulation (120 min) because CA secretion was markedly increased in response to the nicotinic agonist dimethylphenylpiperazinium (DMPP). 5. Capsaicin pre-treatment reduced CA secretion evoked by prolonged field stimulation and the facilitatory action of SP on CA secretion lasted longer in these capsaicin-pre-treated rats than in controls, indicating that SP-containing capsaicin-sensitive fibres innervating the adrenal medulla may be involved in the regulation of CA secretion. 6. In parallel with the increase in CA secretion, 3H overflow from the splanchnic nerve pre-labelled with [3H]choline was also increased by SP. The increase in CA secretion by SP lasted longer than the increase in 3H overflow. These results suggest that SP facilitates CA secretion from the adrenal gland at two levels: (1) pre-synaptically by facilitating ACh release from splanchnic nerve terminals, and (2) post-synaptically by modulating the nicotinic secretory response by protection against nicotinic desensitization of secretion. 7. The present studies provide further evidence that endogenous SP in the splanchnic nerve may modulate CA secretion during stress.

Adrenal Glands↗
PubMed1990

Capsaicin-sensitive nerves are required for glucostasis but not for catecholamine output during hypoglycemia in rats.

We have studied the glucose response and catecholamine (CA) response to insulin in the conscious rat to evaluate the role of sensory fibers in these responses in animals pretreated with capsaicin as neonates. In contrast to previous results obtained in anesthetized rats (Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 370: 201-215, 1986; Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 391: 511-526, 1987.), in conscious rats, insulin (1 IU/kg iv) produced only a mild hypoglycemia, which quickly returned to resting levels and caused no significant changes in plasma epinephrine levels. Somatostatin and SMS-(201-995), a somatostatin analogue, both potentiated and prolonged the insulin-induced hypoglycemia, resulting in an increase in circulating CA levels that was suppressed by hexamethonium and atropine. In capsaicin-pretreated rats the blood glucose levels at 90 min after insulin were significantly lower than those in vehicle-pretreated rats both in the presence (1 IU/kg insulin, 48 +/- 6 vs. 92 +/- 6 mg/100 ml, P less than 0.01) and absence (10 IU/kg insulin, 38 +/- 4 vs. 51 +/- 2 mg/100 ml, P less than 0.01) of SMS-(201-995). The CA levels in capsaicin-pretreated rats at 90 min after insulin were higher than in vehicle-pretreated rats (epinephrine levels: 27 +/- 4 vs. 10 +/- 1 pmol/ml in 1 IU/kg insulin, P less than 0.01; 64 +/- 14 vs. 25 +/- 5 pmol/ml in 10 IU/kg insulin, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Vasoactive intestinal peptide stimulates proenkephalin A mRNA expression in bovine adrenal chromaffin cells.

The effects of vasoactive intestinal peptide (VIP) and substance P (SP) on the amount of proenkephalin A (ProEnk A) mRNA in cultures of bovine adrenal chromaffin cells were examined. Exposure of chromaffin cells to 5 microM VIP for 24 h produced a significant elevation in ProEnk A mRNA. The stimulatory effect of VIP could be abolished by the presence of the calcium channel blocker D600 or actinomycin D but was not affected by the nicotinic antagonist hexamethonium. The results suggest that VIP may induce transcription of ProEnk A mRNA by a Ca2+-dependent, non-cholinergic mechanism. By contrast, SP (5 microM) had no effect on the amount of ProEnk A mRNA. Since VIP is found in nerve terminals and the ganglion cells within the adrenal medulla, this peptide could be an endogenous regulator of adrenal enkephalin gene expression.

Adrenal Medulla↗
PubMed1989

Induction of phenylethanolamine N-methyltransferase mRNA expression by glucocorticoids in cultured bovine adrenal chromaffin cells.

The effects of glucocorticoids on the expression of phenylethanolamine N-methyltransferase (PNMT) mRNA and proenkephalin A (ProEnk A) mRNA in cultures of bovine adrenal chromaffin cells were examined. The expression of PNMT mRNA (approx. 1.1 kilobases) was induced in the presence of glucocorticoids. This induction was of high potency with an EC50 in the range of 1-10 nM for dexamethasone, and was blocked by high concentrations of the glucocorticoid antagonist RU-38486. Cortisol, prednisolone and Reichstein substance S (11-deoxy-17-hydroxycorticosterone) were all effective in stimulating PNMT mRNA expression while cortisone, progesterone and beta-estradiol were without effect. These results indicate that the effects are mediated by specific glucocorticoid receptor activation and exhibited a strict structural requirement for the ability of glucocorticoids to induce PNMT mRNA expression. By contrast, glucocorticoids had no significant effect on the expression of ProEnk A mRNA. In summary, this study provides evidence that glucocorticoids act to regulate PNMT (but not ProEnk A) at the transcriptional level. This differential effect of glucocorticoids suggests that different mechanisms govern the expression of mRNAs required for synthesis of the co-stored secretory components, the enkephalins and adrenaline within the chromaffin cells of the adrenal medulla.

Adrenal Glands↗