Biomedical subjects

M Takiyyuddin

Publications and source records attributed to M Takiyyuddin.

3 recordsLinked to original sources

PubMed1991

A proposed role for chromogranin A as a glucocorticoid-responsive autocrine inhibitor of proopiomelanocortin secretion.

Chromogranin A (CgA) is a 50 kilodalton (kDa) acidic glycoprotein that is costored and cosecreted from secretory granules with endogenous hormone from diverse endocrine cell types. The physiological role(s) of CgA is yet to be defined. In this study we used the AtT-20 mouse corticotropic cell line, which produces both CgA and POMC-derived peptides, to study 1) the regulation of CgA and POMC synthesis and secretion, and 2) the influence of CgA on POMC secretion. To study regulation of CgA and POMC biosynthesis and secretion, cells were treated with dexamethasone (DEX) or CRF for 48 h and CgA and POMC messenger RNAs and proteins were analyzed. Exposure to DEX for 48 h (10 nM) inhibited secretion of the 16 K fragment of POMC by 60% while stimulating CgA secretion 500% of control value. Consonant with these changes in protein, POMC mRNA levels fell to 40% of control levels while CgA mRNA levels increased to 250% of control values with DEX treatment. DEX treatment had no effect on the sizes of the CgA [2.1 kilobase (kb)] and POMC (1.0 kb) mRNAs. CRF (100 nM) stimulated secretion of both CgA (4-fold) and ACTH (2.5-fold) above basal values. By contrast, CRF increased POMC mRNA levels but had no effect on levels of CgA mRNA. Changes in total peptide production paralleled the changes in mRNA levels. Because DEX differentially regulated CgA and POMC synthesis and secretion, we questioned whether CgA could function as an autocrine inhibitor of hormone secretion. CgA inhibited CRF-stimulated secretion of 16 K fragment in a concentration-dependent manner (100% at 100 nM) without affecting basal 16 K fragment secretion. Moreover, anti-CgA antiserum, but not nonimmune serum, increased basal 16 K fragment secretion 2-fold and CRF-stimulated 16 K fragment secretion 1.5-fold. These results suggest that CgA plays an autocrine role as a glucocorticoid responsive inhibitor of POMC-derived peptide secretion.

Animals↗

PubMed1989

Behaviour and hypertension: a pathophysiological puzzle.

Patients with borderline hypertension typically show enhanced sympathetic and decreased parasympathetic tone, characteristic personality traits (submissiveness, hostility) and hyperreactivity to mental stress. It has been proposed that the hypertensive personality results in a persistent 'defence reaction', enhancing sympathetic outflow from the central nervous system and reactivity to stress. But evidence from pharmacological intervention trials suggests that blood pressure reactivity is controlled independently of average baseline blood pressure. A study comparing the effects of the centrally-acting alpha 2-agonist, clonidine, and the selective beta 1-blocker, atenolol, demonstrated that both drugs had a comparable antihypertensive action on baseline blood pressure. However, neither agent affected stress responses to mental arithmetic, submaximal isometric handgrip exercise or cold pressor testing. We conclude that studies of stress reactivity, while of interest to students of circulatory control, are unlikely to yield insights into the causes of human hypertension.

Arousal↗

PubMed1987

Antihypertensive and hypotensive effects of atrial natriuretic factor in men.

Synthetic atrial natriuretic factor (ANF) was administered in ascending doses (0.03, 0.20, 0.45 microgram/kg/min) to eight mildly essential hypertensive men on high (200 mEq/day) or low (10 mEq/day) sodium diets. Responses of blood pressure, heart rate, urinary volume and electrolyte excretion, renin, and aldosterone were measured. For the entire group, ANF lowered blood pressure and increased heart rate during the 0.20 and 0.45 microgram/kg/min infusions, and the antihypertensive effect of the peptide persisted for at least 2 hours after the infusions ended. Four patients (2 at 0.20 microgram/kg/min and 2 at 0.45 microgram/kg/min) experienced sudden bradycardia and hypotension at the end of or shortly after completion of ANF infusion. Renal excretion of water, sodium, chloride, calcium, and phosphorus increased in a dose-dependent fashion in response to infused ANF. Patients on the 200 mEq/day sodium diet had greater increases in urinary volume (11.1 +/- 2.8 vs 3.0 +/- 2.0 ml/min; p less than 0.05), sodium (870 +/- 134 vs 303 +/- 27 microEq/min; p less than 0.05), and chloride (801 +/- 135 vs 176 +/- 75 microEq/min; p less than 0.02) compared with patients on the low sodium diet. The apparent direct suppressive effect of a 0.03 microgram/kg/min infusion of ANF on renin and aldosterone levels was overcome at higher doses by counterregulation provoked by the depressor action. Renin was slightly (-12%) suppressed during the 0.03 microgram/kg/min infusion of ANF but increased at the 0.20 (+50%) and 0.45 microgram/kg/min (+90%; p less than 0.03) rates. Aldosterone declined significantly during the 0.03 microgram/kg/min infusion (-45%; p less than 0.01) of ANF but not during the two higher dose infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗