Short-term Administration Of Growth Hormone Research Articles

Short-Term Growth Hormone Administration Mediates Hepatic Fatty Acid Uptake and De Novo Lipogenesis Gene Expression in Obese Rats

Obesity has been linked to metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Obesity causes a decrease in growth hormone (GH) levels and an increase in insulin levels. Long-term GH treatment increased lipolytic activity as opposed to decreasing insulin sensitivity. Nonetheless, it is possible that short-term GH administration had no impact on insulin sensitivity. In this study, the effect of short-term GH administration on liver lipid metabolism and the effector molecules of GH and insulin receptors were investigated in diet-induced obesity (DIO) rats. Recombinant human GH (1 mg/kg) was then administered for 3 days. Livers were collected to determine the hepatic mRNA expression and protein levels involved in lipid metabolism. The expression of GH and insulin receptor effector proteins was investigated. In DIO rats, short-term GH administration significantly reduced hepatic fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) mRNA expression while increasing carnitine palmitoyltransferase 1A (CPT1A) mRNA expression. Short-term GH administration reduced hepatic FAS protein levels and downregulated gene transcription of hepatic fatty acid uptake and lipogenesis, while increasing fatty acid oxidation in DIO rats. DIO rats had lower hepatic JAK2 protein levels but higher IRS-1 levels than control rats due to hyperinsulinemia. Our findings suggest that short-term GH supplementation improves liver lipid metabolism and may slow the progression of NAFLD, where GH acts as the transcriptional regulator of related genes.

Beneficial Effects of Short-Term Growth Hormone Administration on Non-Alcoholic Fatty Liver Disease (NAFLD) in Obese Rats

Beneficial Effects of Short-Term Growth Hormone Administration on Non-Alcoholic Fatty Liver Disease (NAFLD) in Obese Rats

The effects of short term growth hormone administration and resistance training on the histopathology and mutation of the BRAF gene (T1799A) in thyroid tissue of the brown rat (Rattus norvegicus).

The effects of short term growth hormone administration and resistance training on the histopathology and mutation of the BRAF gene (T1799A) in thyroid tissue of the brown rat (Rattus norvegicus).

Growth Hormone (GH) and Cardiovascular System.

This review describes the positive effects of growth hormone (GH) on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on vessels improving oxidative stress imbalance and endothelial dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease, inducing a neovascularization process that finally increases flow in ischemic tissues. We include some preliminary data from a trial in which GH or placebo is given to elderly people suffering from critical limb ischemia, showing some of the benefits of the hormone on plasma markers of inflammation, and the safety of GH administration during short periods of time, even in diabetic patients. We also analyze how Klotho is strongly related to GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH, most likely to repair the injury in the ischemic tissues. We also show how GH can help during wound healing by increasing the blood flow and some neurotrophic and growth factors. In summary, we postulate that short-term GH administration could be useful to treat cardiovascular diseases.

Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength

Introduction Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism. Materials and methods Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5 mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly. Results bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets. Conclusion These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake.

GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD‐INDUCED LEFT VENTRICULAR HYPERTROPHY

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy. 2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis. 3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group. 4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

The potential of hormones and selective oestrogen receptor modulators in preventing voiding dysfunction in rats

To investigate whether oestrogen, selective oestrogen receptor modulators (SERMs), and growth hormone (GH) can prevent the development of voiding dysfunction in a postpartum postmenopausal rat model of voiding dysfunction. Immediately after spontaneous delivery, nine primiparous Sprague-Dawley rats served as uninjured controls (sham group) and 54 underwent intravaginal balloon dilation. On day 7, the 54 subject rats underwent bilateral ovariectomy. A week later, six treatment groups of nine rats were randomized to receive: normal saline (injured control group), 17beta-oestradiol (E(2)), raloxifene, levormeloxifene, GH, or GH + E(2). The treatment groups received daily subcutaneous injections for 3 weeks. The effects of hormone treatment were examined by conscious cystometry at the end of the study. Voiding dysfunction was defined to include overactive bladder and sphincter deficiency. The sham rats had a mean (sd) voiding frequency of 3 (0.87) times in 10 min and a bladder capacity of 0.43 (0.13) mL with smooth cystometry curves. The number of rats in each treatment group (each group contained nine rats) that had voiding dysfunction was as follows: E(2), three; raloxifene, six; levormeloxifene, four; and controls, four (P > 0.05 among the groups). Only one rat in the GH-treated group and no rats in the GH + E(2)-treated group had voiding dysfunction, which was significantly less in the GH + E(2)-treated group than in the controls (P = 0.041). This functional data suggest that the development of voiding dysfunction can be prevented by short-term administration of GH and GH + E(2) in our rat model. SERMs and E(2) alone seem to have no therapeutic effect.

Short-term administration of growth hormone (GH) lowers blood pressure by activating eNOS/nitric oxide (NO)-pathway in male hypophysectomized (Hx) rats

BackgroundThe aim of the study was to evaluate the acute and continuous (up to 14 days of treatment) effect of growth hormone (GH) on blood pressure (BP) regulation and to investigate the interplay between GH, nitric oxide (NO) and BP.In un-supplemented and GH supplemented hypophysectomized (Hx) male rats as well as intact rats, continuous resting mean arterial blood pressure (MAP) was measured using telemetry. Baroreceptor activity and the influences of NO on BP control were assessed during telemetric measurement. Furthermore, basal plasma and urine nitrate levels and aortic endothelial nitric oxide synthase (eNOS) expression were analysed. Endothelial function as well as vascular structure in the hindquarter vascular bed was estimated using an in vivo constant-flow preparation.ResultsHypophysectomy was associated with decreased MAP (Hx: 83 ± 3 vs Intact: 98 ± 6 mmHg, p < 0.05) and heart rate (HR) (Hx: 291 ± 4 vs Intact: 351 ± 7 beat/min, p < 0.05). Endothelial dysfunction and reduced vasculature mass in the hindquarter vascular bed was found in Hx rats. GH substitution caused a further transient decrease in MAP and a transient increase in HR (14% and 16% respectively, p < 0.05). The reduction in MAP appeared to be NO dependent. Aortic eNOS expression was unchanged. GH substitution resulted in an impaired baroreceptor function. Two weeks of GH treatment did not normalise the BP, vascular structure and the endothelial function in the resistance vessels.ConclusionGH substitution seems to have a short lasting effect on lowering blood pressure via activation of the NO-system. An interaction between GH, NO-system and BP regulation can be demonstrated.

Long-Term Outcome of Growth Hormone Therapy in Children and Adolescents

Growth hormone (GH) has been available for more than 4 decades for the treatment of GH deficiency. Initially, GH was extracted from the pituitary glands of human cadavers, but its use was discontinued following the transmission of the Creutzfeldt-Jakob virus. After the development of recombinant GH (somatropin) in 1985, an 'unlimited' commercial source of GH has been available, allowing for the treatment of a large number of short GH-deficient and -sufficient children. Refinements in both the dosage and the frequency of administration of GH have allowed GH-deficient children to reach nearly normal final heights, although mostly they are still below their target heights. Decreased bone mineral densities and increased concentrations of fasting and postprandial lipids, coagulation factors, and several independent cardiovascular risk factors have been reported in GH-deficient children and adolescents and appear to improve with GH administration. The short-term administration of GH to mostly non-GH-deficient short children with Turner syndrome, chronic renal insufficiency (CRI), intrauterine growth retardation (IUGR), and idiopathic short stature (ISS) has resulted in increased growth velocities. In addition, the final height of patients with Turner syndrome and CRI appears to improve with the long-term administration of GH. Final height data are still lacking in adolescents with IUGR, but height standard deviation score and final height predictions appear to improve with therapy. Based on the incomplete and inconclusive available data, one must conclude that GH treatment of children with ISS cannot be advised. The use of GH at replacement doses in children with GH deficiency has resulted in rare and generally reversible adverse effects. The long-term administration of pharmacologic GH doses to short, mostly non-GH-deficient children must, however, still be viewed with caution, as long-term complications cannot as yet be fully evaluated. GH therapy must be individualized and should be limited only to children with severe short stature or a significantly decreased growth velocity, to children under considerable stress due to their short stature, and to patients in whom low GH or low insulin-like growth factor-1 secretion might be the rate-limiting factors for growth. The cost of the medication and the inconvenience of daily GH injections to otherwise mostly healthy short children must also be taken into account.

Growth hormone therapy during neonatal hypoxia in rats: body composition, bone mineral density, and insulin-like growth factor-1 expression.

Hypoxia from birth results in a decrease in body weight gain, body size, and bone mineral density (BMD). The purpose of the present study was to determine whether short-term administration of growth hormone (GH) (rat GH; 100 microg/d) could attenuate some of these effects of neonatal hypoxia. Rat pups (with their lactating dams) were exposed to hypoxia (vs normoxic control) from birth. Hypoxia was continued until 14 d of age, with rat GH (vs vehicle control) administered daily. Hypoxia significantly inhibited body weight gain; GH therapy did not reverse this effect. GH therapy did reverse the inhibitory effect of hypoxia on tail length but not on body length. Hypoxia decreased BMD analyzed by dual X-ray absorptiometry (DXA); this effect was not reversed by GH therapy. Both GH therapy and hypoxia decreased the percentage of body fat analyzed by DXA, the effects of which were additive when combined. There were minimal effects of hypoxia and GH therapy on plasma insulin-like growth factor-1 (IGF-1), IGF-binding protein-3, and hepatic IGF-1 mRNA expression. We conclude that some of the effects of hypoxia on body habitus are reversed by GH therapy, but that short-term GH therapy did not prevent a loss of BMD. GH therapy for more than 14 days may be necessary to appreciate fully its potential in the treatment of the sequelae of neonatal hypoxia.

Time course of the response to recombinant growth hormone in acidotic mice.

Long-term administration of recombinant growth hormone (GH) increases growth, despite persistent acidosis, in mice with carbonic anhydrase II deficiency (CAD). In contrast, short-term administration of GH to acidotic rats fails to improve growth. To determine the factors affecting the rate of growth response to GH in acidosis, we analyzed serial measurements obtained during a randomized trial of GH in CAD mice and healthy controls. Administration of GH increased standardized growth progressively up to 5-9 weeks. These data suggest that assessment of the response to GH in rodents requires prolonged administration.

Effects of short-term administration of growth hormone in healthy young men, women, and women taking oral contraceptives.

Effects of short-term administration of growth hormone (GH) with respect to gender and oral contraceptives (OCs) were investigated in healthy young adults. Open, prospective 2-week study. Clinical research centre, university hospital. Three groups of healthy young adults were included: six men, six women with normal menstrual cycles, and six women taking OCs. The subjects were given recombinant human GH subcutaneously for 2 weeks: 1 U m-2 body surface daily during the first week, and 3 U m-2 daily during the second week. Serum samples were drawn in the morning after overnight fasting on days 0, 3, 7, 10 and 14, and were analysed for GH, insulin-like growth factor 1 (IGF-1), insulin, testosterone, sex hormone-binding globulin (SHBG), lipids and markers of bone metabolism. Second-void morning urine was analysed for deoxypyridinoline (Dpyr). During administration of GH, serum IGF-1 increased in the men and in the women without OCs (86 and 52%, respectively). In the OC women, IGF-1 did not change significantly. Serum insulin increased in all three groups, with the largest change (122%) in the men and the smallest (47%) in the OC women. Blood glucose was unchanged. Total cholesterol, low-density lipoprotein (LDL) cholesterol and the LDL/high-density lipoprotein cholesterol ratio were reduced in the men only. Biochemical markers of bone resorption (serum procollagen type I, urinary Dpyr) increased in the men, and markers of bone formation (serum osteocalcin and telopeptide of collagen type I) increased in the men as well as in the women not taking OCs. The testosterone/SHBG ratio increased in the men on account of a reduction in SHBG. The response to short-term administration of GH differed in the three groups, with the largest effect in the men and the smallest in the OC women. The inhibitory influence of contraceptives underlines the role of sex steroids in modulating the susceptibility to GH.

Short-Term Growth Hormone Administration at the Time of Opportunistic Infections in HIV-Positive Patients

Short-Term Growth Hormone Administration at the Time of Opportunistic Infections in HIV-Positive Patients

Insulin-like growth factor (IGF-I), IGF-bindingprotein and the acid-labile subunit responses to short-term growth hormone administration in paediatric patients with liver disease

Insulin-like growth factor (IGF-I), IGF-bindingprotein and the acid-labile subunit responses to short-term growth hormone administration in paediatric patients with liver disease

Fatty acid synthesis in lambs in vivo as affected by nutrition and hormone administration

Fatty acid (FA) synthesis was studied in lambs in vivo using the incorporation of tritium from tritiated water into FA under a number of experimental conditions. Expt 1 investigated the use of a high dose of tritiated water, with slaughter of the sheep after 4 h, and showed that sampling of tail fat was sucient as an index of the activity in carcass fat. Calculations of FA synthesised demonstrated the relative amounts contributed by carcass and offal. Extrapolation to a time of 24 h, assuming linearity of incorporation of tritium with time, gave results that were similar to what would be expected from the gains in body weight. Restriction of feed intake reduced the amount of FA synthesis. Expt 2 demonstrated that incorporation of tritium into FA was almost linear over 24 h after an initial delay (mixing time) and there was probably no redistribution of tritiated FA between tissues. The increased time for incorporation had 3 major advantages: the dose of tritiated water could be reduced to more manageable levels, the error due to mixing time was reduced, and the measurement of synthesis was integrated over 24 h. Expt 3 showed that increasing feed intake above 24 g/kg liveweight, which was close to maintenance, resulted in progressive increases in FA synthesis, measured by the technique of Expt 2 over 24 h. Incorporation of tritium into FA and non-saponifiable lipids, including cholesterol, in liver increased with feed intake in a sigmoid curve, with a maximum rate of change around an intake of 30 g/kg. This reflected the release of FA via lipoproteins into the circulation. The specific activity of the FA in the liver was similar to that of the ruminal FA and suggested that there was no actual synthesis in the liver. Expt 4 investigated the effects of growth hormone (GH), oestradiol, andff Triton WR1339 administration to lambs on FA synthesis following short-term administration of GH at 0·3 mg/lamb·day, oestradiol (120 µg on Day 1 and 3), or Triton WR1399. Growth hormone caused a significant reduction in FA synthesis/g FA (P &lt; 0·05) and in FA synthesis/106 cells in subcutaneous fat (P &lt; 0·01) after 4 days of administration. There was a reduction in cell diameter and number of fat cells/g FA (P &lt; 0·05). Oestradiol showed a tendency to cause increased FA synthesis; there was a significant effect of treatment (P &lt; 0·01) in omental fat. FA synthesis was significantly increased in the group of lambs given oestradiol by comparison with the group given GH (P &lt; 0·01), whereas Triton WR1399 had no effect on FA synthesis in adipose tissue, substantiating that liver and plasma lipoproteins contribute only low amounts of FA to subcutaneous fat. Expt 5 further investigated the effects of administration of GH for 1 or 4 days to lambs on high-grain pellets consumed at high intakes (57 g/kg liveweight). GH had no effect, irrespective of how the results were expressed, but rates of FA synthesis were &gt;10-fold higher than those in Expt 4. In both trials, plasma levels of GH were raised and plasma levels of insulin-like growth factor-1 indicated that GH was active. These results showed that FA synthesis can be measured in vivo in lambs effectively, and the method should be of more practical use than alternative methods in studies of agents affecting the level of carcass fat. The effects of GH were not as marked as those found in previous studies in pigs because of the short-term administration of GH, but even so, the excess intake of high-grain pellets appeared to prevent any effect of GH.

Different Effects of Continuous and Intermittent Patterns of Growth Hormone Administration on Lipoprotein Levels inGrowth Hormone-Deficient Patients

Background: Lipoprotein (a) (Lp(a)) is a risk marker for the development of atherosclerotic coronary heart disease. Growth hormone (GH) administration to GH-deficient (GHD) adults increases serum Lp(a) concentrations, and the levels of Lp(a) and GH are correlated in patients with acromegaly. Studies in rats have demonstrated differential effects of constant and intermittent GH patterns on levels of certain lipoproteins. The aim of the present studies was to describe the impact of intermittent and continuous patterns of GH delivery to GHD patients on serum levels of Lp(a) and other lipoproteins. Methods: In one study (A) 10 GHD patients received in random order a fixed GH dose intravenously as: (1) continuous infusion; (2) eight bolus injections, and (3) a combination of 1 and 2. Each study lasted 36 h and was preceded by at least 4 weeks without GH. In another study (B) 13 GHD patients received GH in random order as: (1) continuous subcutaneous (s.c.) infusion, and (2) daily s.c. injections in the evening for 1 month each. The patients were studied during steady-state conditions at the end of each treatment period. Results: In study A Lp(a) levels increased significantly following continuous (p < 0.05) and combined patterns (p < 0.02) of GH administration to GH-deprived GHD patients, whereas the increase after GH bolus injections alone was not significant (p = 0.14). In study B significantly higher (p < 0.05) serum levels of Lp(a) were obtained after continuous s.c. infusion as compared with daily s.c. injections of GH. Concentrations of the high-density lipoprotein (HDL) cholesterol were significantly lower (p < 0.02) after the continuous GH pattern. Similarly, the HDL fraction Apo A-1 tended to be lower with constant GH delivery (p = 0.052). Serum levels of total cholesterol, triglyceride and Apo B were similar on the two occasions. Conclusion: Short-term GH administration to GH-deprived GHD patients increased serum Lp(a), but only significantly with continuous delivery. During more prolonged GH exposure, constant s.c. infusion of GH resulted in slightly raised Lp(a) levels and reduced HDL and Apo A1 levels as compared with intermittently administered GH. The findings are consistent with the more effective induction of serum IGF-I levels after continuous patterns of GH delivery previously reported in GHD patients. Longer-term data are needed before conclusions with respect to the impact of the pattern of GH administration on, e.g., the risk of developing coronary heart disease can be drawn.

Gender differences in sensitivity to short-term administration of growth hormone (GH) in healthy young adults

Gender differences in sensitivity to short-term administration of growth hormone (GH) in healthy young adults

Water and Sodium Retention during Short-Term Administration of Growth Hormone to Short Normal Children

GH treatment of adult patients with GH deficiency (GHD) or healthy volunteers results in weight gain and fluid and sodium retention. In the present study we have challenged normal short children with dehydration and water load, and evaluated their water and sodium clearance, plasma renin activity (PRA) and aldosterone over 4 weeks of GH administration. Eleven prepubertal short normal children, aged 4–9 years, were the subjects of this study. Recombinant GH was administered daily at a dose of 2.5 units/m². Dehydration and water load experiments were conducted before GH (day 0) and on days 3, 7 or 28 of GH. An initial 15-hour fast ended with a 3-hour urine collection. A tap-water load of 800 ml/m² was given orally. Urinary volumes were followed hourly for 3 h, as were urinary and serum creatinine, Na, K, aldosterone, plasma osmolality and PRA. Before GH therapy the subjects excreted within 2 h a mean 42% and within 3 h a mean 65% of the load. After 3 days of GH therapy the same children retained water significantly and excreted only 22 (p < 0.02) and 45% (p < 0.05) of the load volume, respectively. Calculating the free water clearance revealed no effect of GH therapy, whereas the fractional excretion of sodium and potassium decreased significantly by day 3 of GH administration, along with an increase in PRA and serum aldosterone. All these changes normalized by days 7 and 28 of GH therapy. It is concluded that short-term administration of GH to short normal children results in a transitory mild retention of sodium and a secondary water retention, and suggests that the primary event leading to sodium retention during the early phase of GH therapy of short normal children is an inappropriate increase in PRA.

Growth Hormone: A Physiological Fountain of Youth?

During childhood and early adult life, growth hormone (GH), secreted by the anterior pituitary, is involved in the growth of bones and muscles and other organs as well. Aging is characterized by a decrease in muscle mass and bone strength and an increase in adipose, similar to the effects of pathological hyposecretion of GH in the young. Aging is also accompanied by a gradual decrease in the output of GH, like the drying of an internal fountain, until in the eighth decade of life, it is secreted at less than one-fifth of the youthful level. The GH hypothesis of aging posits that with the availability of human recombinant growth hormone and human recombinant insulin-like growth factor-I, which mediates most of the effects of GH, the GH hypothesis has become testable. Initial experiments involving short term administration of GH in a group of elderly men did indeed show modest improvement in lean body mass and adipose tissue. These studies are sometimes—and incorrectly—taken as proof of the correctness of...

Involvement of both calcium influx and calcium mobilization in growth hormone-induced [Ca 2+] i increases in Chinese hamster ovary cells

This study reports rapid effects of growth hormone (GH) on the intracellular free calcium concentration ([Ca 2+] i) in Chinese hamster ovary (CHO) cells stably expressing rabbit GH receptor. [Ca 2+] i was measured by spectrofluorimetric methods in single cells and membrane Ca 2+ currents by patch clamp techniques in the whole-cell configuration. In individual CHO cells, bathed in a standard saline solution containing 2 mM Ca 2+, basal [Ca 2+] i was 191±27 nM (mean ±S.D.; n=83). Short term administration of GH (100 ng/ml, 30 s) induced a [Ca 2+] i increase in 54% of cells tested ( n=398 of 743). Responses were clearly heterogeneous. Maximum calcium increase varied from 16 to 853 nM and time to peak varied from 4 to 320 s. On examination of the [Ca 2+] i increases, it was possible to define two different types of calcium responses to GH. Experimental manipulations of extracellular and intracellular calcium concentrations demonstrated that GH-induced calcium increases involved both calcium influx and calcium mobilization. Calcium influx, a long lasting, small amplitude (63±34 nM) response, was observed in 121 out of 398 cells (30%) whereas calcium mobilization, a transient, large amplitude (263±175 nM) response, was observed in 277 out of 398 cells (70%). Moreover, patch clamp data show that influx did not involve the dihydropyridine-sensitive calcium channels.