Effect of secretin and glucagon on Brunner''s gland secretion in the rat

Brunner's gland secretion in response to infusion of secretin and glucagon was studied in the rat. Secretin was infused in doses of 15, 150 and 1500 ng/kg/h. All dose significantly increased bicarbonate and protein output and depleted Brunner's glands of PAS-positive mucin. Bicarbonate secretion was related to plasma secretin concentration, and a marked stimulatory effect of secretin was found in very low, probably physiological, plasma concentrations. Maximal bicarbonate output was obtained at a plasma concentration of secretin about 20 pmol/l. Glucagon was infused at a rate of 1.0 micrograms/kg/h and did not influence secretion rate or cell morphology. Also large doses of 5.0 and 50.0 micrograms/kg/h had no effect on Brunner's gland secretion. It is concluded that secretin in very low plasma concentrations stimulates secretion of bicarbonate, protein and mucus from Brunner's glands in the rat, while glucagon has no effect, and it is suggested that secretin may be involved in the physiological regulation of Brunner's gland secretion.     

Epidermal growth factor inhibits cysteamine-induced duodenal ulcers

The effect of the duodenal ulcerogen cysteamine on secretion of epidermal growth factor from Brunner's gland pouches was studied in the rat. Total output of immunoreactive epidermal growth factor was reduced to approximately 55%, compared with controls, 5 h after administration of cysteamine (300 mg/kg, s.c.). Furthermore, measurements on tissue extracts of the pouches revealed that 5 h after cysteamine treatment, Brunner's glands were depleted of epidermal growth factor. The effect on ulcer development of intraduodenally applied exogenous epidermal growth factor (1 micrograms/kg . h) also was studied. Luminal epidermal growth factor significantly inhibited the formation of cysteamine-induced duodenal ulcer, compared with controls receiving saline. The effect was not due to inhibition of gastric acid secretion or stimulation of duodenal bicarbonate secretion since the dose of epidermal growth factor used, when tested on chronic fistula rats, had no effect on acid secretion and did not influence bicarbonate secretion from Brunner's gland pouches. These results demonstrate that epidermal growth factor has a cytoprotective effect on the duodenal mucosa, and it is suggested that inhibition of synthesis and secretion of endogenous epidermal growth factor may be a pathogenetic factor in cysteamine-induced duodenal ulcer.     

Adrenergic effects on secretion of epidermal growth factor from Brunner's glands.

The influence of the sympathetic nervous system and adrenergic agonists on flow rate and secretion of epidermal growth factor (EGF) from Brunner's glands has been investigated in the rat. Chemical sympathectomy by administration of 6-hydroxydopamine increased volume secretion and output of EGF from Brunner's glands but depleted the glands of EGF. Infusion of noradrenaline, an alpha-adrenergic agonist, inhibited basal and vasoactive intestinal polypeptide (VIP) stimulated flow rate and output of EGF from Brunner's glands and increased the amount of EGF in the tissue. Vasoactive intestinal polypeptide also increased the amount of EGF in Brunner's gland tissue and this was unchanged after simultaneous infusion of VIP and noradrenaline as well as VIP and isoproterenol, a beta-adrenergic agonist. Isoproterenol had no effect on basal and VIP stimulated secretion of EGF from Brunner's glands. The presence of PAS-positive mucus in Brunner's glands was unchanged during infusion of noradrenaline whereas VIP induced a depletion of Brunner's gland mucus which in turn was prevented by simultaneous infusion of noradrenaline. This study indicates that the sympathetic nervous system influence the volume secretion, output of EGF and mucus content in Brunner's glands probably by activation of alpha-adrenergic pathways.     

Effect of secretin and somatostatin on secretion of epidermal growth factor from brunner's glands in the rat

The effect of secretin and somatostatin on secretion of epidermal growth factor (EGF) from Brunner's glands was investigated in rats. Secretin increased volume secretion and the median output of EGF rose from 720 fmol/5 hr (total range 460–1320) in controls to 2065 fmol/5 hr (total range 1560–2730) at a dose of 50 pmol/kg/hr of secretin. Somatostatin inhibited Brunner's gland secretion, but the total output of EGF remained unchanged. Secretin-stimulated volume secretion and secretion of EGF was significantly reduced by simultaneous infusion of somatostatin. This study has shown that secretin stimulates secretion of EGF as well as volume secretion from Brunner's glands. Somatostatin prevents the effect of secretin on Brunner's glands, which suggests a role for somatostatin in control of Brunner's gland secretion.     

Vasoactive intestinal polypeptidergic nerves and Brunner's gland secretion in the rat

Vasoactive intestinal polypeptide is known to have powerful effect on the secretions from endocrine and exocrine glands. By immunohistochemical studies on the rat, both a dense network of vasoactive intestinal polypeptide-immunoreactive nerve fibers around the acini of Brunner's glands, and small ganglia with vasoactive intestinal polypeptide-immunoreactive nerve-cell bodies close to the glands were demonstrated. Intravenous infusions of vasoactive intestinal polypeptide in doses of 10, 100, and 1000 ng/kg.h significantly increased flow rate, as well as bicarbonate and protein output from Brunner's glands in the rat. After infusion of vasoactive intestinal polypeptide the secretory cells, which in the control group were rich in PAS-positive mucin, became almost completely PAS-negative. It is suggested that physiologic secretion from Brunner's glands may be stimulated by the vasoactive intestinal polypeptidergic nerves.     

Endogenous nitric oxide mediates pancreatic exocrine secretion stimulated by secretin and cholecystokinin in rats

Nitric oxide (NO) is one of the important biologic mediators in regulation of gastrointestinal (GI) functions, but the influence of NO on the release of secretin and cholecystokinin (CCK) and exocrine pancreatic secretion has not been adequately investigated in the rat. The aim of this study was to determine the role of NO on endogenous and exogenous secretin- or CCK-stimulated pancreatic exocrine secretion both in anesthetized and conscious rats. Experiments were carried out in four different groups of rats with duodenal pancreatobiliary cannulas and jugular vein catheters. Group 1: During duodenal infusion of 0.05N HCl or 15% casein (pH 7.0), N-nitro-L-arginine (NNA), an inhibitor of NO-synthase in graded doses (2.5, 5, 10 mg/kg/h), was infused intravenously. Group 2: One hour after starting intravenous secretin at 5 pmol/kg/h or intravenous CCK-8 at 0.06 microg/kg/h, NNA in graded doses was administered intravenously. Group 3: In conscious rats, NNA (5 mg/kg/h) was given intravenously for 1 hour after a meal. Group 4: L-Arginine at 100 mg/kg/h was infused intravenously during the period of NNA (5 mg/kg/h) infusion in groups 1, 2, and 3. Pancreatic juice was collected at 30-minute intervals to measure volume, as well as output of bicarbonate and protein. At the end of the experiment, plasma secretin, vasoactive intestinal polypeptide (VIP) and CCK levels were determined by radioimmunoassay (RIA). NNA dose dependently inhibited the pancreatic secretion of fluid and bicarbonate stimulated by duodenal acidification, exogenous secretin, and a meal. NNA dose dependently inhibited the pancreatic secretion of protein stimulated by duodenal infusion of casein, exogenous CCK, and a meal. L-Arginine significantly reversed the NNA-induced inhibition of pancreatic secretion in all experiments. NNA did not alter significantly the plasma levels of secretin, VIP, and CCK. Our results indicated that endogenous NO plays a significant role in the regulation of pancreatic exocrine secretion stimulated by secretin and CCK. However, NO does not influence the release of secretin, VIP, or CCK in the rat.     

Effects of somatostatin and pancreatic polypeptide on exocrine and endocrine pancreas in the rats

The effects of somatostatin-14 (SS) and rat pancreatic polypeptide (rPP) on endocrine and exocrine functions of the pancreas, stimulated by 40 ng/kg cholecystokinin octapeptide during continuous infusion of 1 U/kg/h secretin, were investigated in the rat, in vivo. Protein output in the pancreatic juice and integrated insulin (IRI) secretion were inhibited, in a dose related fashion, by continuous infusion of SS, in doses of 0.5, 5 and 50 micrograms/100g/h. On the other hand, bicarbonate and volume output were not inhibited by SS. The rPP significantly inhibited not only the protein output but also the bicarbonate and volume output of the pancreatic juice in doses of 0.1 and 1 microgram/100g/h. Integrated IRI secretion was inhibited significantly by rPP, but the inhibition of IRI secretion was much greater in the portal than in the jugular vein. Plasma SS and rPP concentrations showed physiological ranges during infusion of doses of 0.5 and 0.1 microgram/100g/h of SS and rPP, respectively. Therefore, there was a marked difference between the inhibition by rPP and that by SS on the exocrine and endocrine pancreas. These observations suggest that SS and PP may play a physiological role in the pancreas and that their effects on the pancreas relate to different mechanisms.     

Is somatostatin a humoral regulator of the endocrine pancreas and gastric acid secretion in man?

The effect of low dose infusions of somatostatin on meal stimulated gastric acid secretion was studied in eight healthy volunteers by intragastric titration after a peptone test meal with radioimmunoassay control of the plasma concentrations of somatostatin and the pancreatic hormones glucagon and insulin. Infusion of somatostatin in a dose of 100 ng/kg/h, resulting in a plasma concentration of 13.4 +/- 2.1 pmol/l, inhibited acid secretion significantly, and in a dose of 800 ng/kg/h, with corresponding plasma concentration of 66.5 +/- 12.0 pmol/l the acid secretion was virtually abolished. Plasma concentrations of insulin and pancreatic glucagon decreased significantly during infusion of 200 ng/kg/h (24.5 +/- 7.5 pmol/l) and glucose concentrations increased. Serum gastrin was only significantly decreased during the highest dose of somatostatin. The range of plasma somatostatin concentrations obtained with the lower doses correspond to reported physiological variations. The results support the concept that somatostatin participates in the hormonal control of the pancreatic endocrine and the acid secretion.     

Somatostatin analog, SMS 201-995, inhibits pancreatic exocrine secretion and release of secretin and cholecystokinin in rats.

We studied the effect of a synthetic octapeptide somatostatin analog, SMS 201-995 (sandostatin), on pancreatic exocrine secretion and on plasma secretin and cholecystokinin (CCK) levels in vivo in anesthetized rats. The exocrine pancreas was stimulated by either intravenous infusion of both secretin (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 micrograms/kg/h) or intraduodenal infusion of oleic acid (pH 6.5) in a dose of 0.25 mmol/h. Intravenous administration of SMS 201-995 in three different doses of 100, 200, and 400 ng/kg/h resulted in dose-related inhibition of pancreatic secretion in terms of volume, bicarbonate, and amylase stimulated by exogenous secretin and CCK. Intraduodenal oleic acid stimulated pancreatic secretion, including volume, bicarbonate, and amylase, and this was accompanied by a significant elevation in the plasma concentrations of secretin and CCK. Intravenous administration of SMS 201-995 in the three different doses described above caused dose-dependent suppression of the increase in pancreatic exocrine secretion as well as the plasma concentration of secretin and CCK induced by intraduodenal infusion of oleic acid. It is concluded that SMS 201-995 inhibits pancreatic exocrine secretion and the release of endogenous hormones, such as secretin and CCK, in rats.     

Effect of peptide YY on gastric acid secretion, gastrin and somatostatin release in the rat

The influence of PYY on stimulated gastric acid secretion and the possible role of gastric somatostatin was measured in rats. PYY, infused intravenously at a dose of 800 pmol/kg/h, reduced pentagastrin (20.8 nmol/kg/h) stimulated gastric acid secretion by 34 +/- 3%, whereas in controls acid secretion remained constant throughout the 90 min observation period. In a second series the effect of PYY on the endogenous gastric somatostatin-like immunoreactivity and gastrin-release was tested in the isolated, vascularly perfused rat stomach. PYY perfused at concentrations of 10 pM to 100 nM did not change either somatostatin or gastrin secretion from the rat stomach in vitro. The study shows that PYY suppressed acid secretion in the rat. Endogenous somatostatin or gastrin is unlikely to mediate the inhibitory effect of PYY on acid production.     

Effects of exogenous insulin, glucagon, and somatostatin on islet hormone secretion in the perfused chicken pancreas

The effects of exogenous insulin were examined in the isolated perfused chicken pancreas with the duodenum excluded. At low background glucose (50 mg/dl), exogenous insulin infused at a concentration of 20,000 microU/ml elicited clear stimulation of somatostatin secretion while simultaneously inhibiting glucagon release. When the background glucose concentration was elevated to 750 mg/dl, exogenous insulin, had no effect on either somatostatin or glucagon release. When graded doses of exogenous insulin were infused into the chicken pancreas at low background glucose, low concentrations (200 microU/ml) had little effect on somatostatin or glucagon release, but higher concentrations (2000 and 20,000 microU/ml) had clear effects on both somatostatin and glucagon secretion. Glucagon infused at 100 ng/ml stimulated both insulin and somatostatin release. When somatostatin was infused at 25 ng/ml, clear inhibition of glucagon was seen with insulin inhibited to a lesser extent. This study supports the notion of a negative feedback relation between B and D-cells of the pancreatic islets and suggests a paracrine mediation.     

Oestradiol, vasoactive intestinal peptide and fibroblast growth factor in the growth of human pituitary tumour cells in vitro

The growth of two human prolactin-secreting cell lines developed in our laboratory has been investigated in response to a number of factors. Oestrogen stimulated the synthesis of DNA and protein and increased prolactin secretion. Dexamethasone had the opposite effect to oestrogen. In the presence of serum, epidermal growth factor (EGF) inhibited cell growth at concentrations of 5 ng/ml. Known secretagogues of prolactin (vasoactive intestinal peptide (VIP), TRH, bombesin and neurotensin) were investigated for their action on cell growth but only VIP had a stimulatory effect. Two preparations of fibroblast growth factor (FGF) were studied. One form, derived from bovine pituitary glands, stimulated human pituitary cell growth. In contrast, another FGF, of the basic type (rFGF), was inhibitory to cell growth, increasing the time for cell doubling from 30 to 72 h. This inhibitory effect of rFGF was modified but not abolished by serum, oestradiol, platelet-derived growth factor or EGF. We conclude that bovine pituitary contains at least two fibroblast growth factors, both of which stimulate fibroblast cell growth, but one stimulates and the other inhibits human pituitary tumour cell growth.     

Action of secretin on pancreatic enzyme secretion in man. Studies on pure pancreatic juice

The action of pure, natural secretin on the pancreatic secretion of enzymes was investigated in six patients with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Secretin infused for five successive 50 minute periods at increasing doses of 0.03, 0.1, 0.3, 0.9 and 2.7 clinical units (CU)/kg/h, produce a dose dependent increase in protein and lipase output. A weak but significant (p less than 0.02) increase of enzyme output above the fasting level was already observed with the lowest dose. The maximal output of protein and lipase, observed with the highest dose of secretin infused, corresponded to about 50% of that induced by maximal doses of cerulein (100 ng/kg/h) plus secretin (1 CU/kg/h). As far as bicarbonate is concerned, the lowest dose of secretin (0.03 CU/kg/h) significantly (p less than 0.001) stimulated bicarbonate output. The dose of 0.9 CU/kg/h of secretin evoked a bicarbonate output of 526 +/- 49 micromol/min; trebling the dose of secretin did not significantly increase the output of bicarbonate above this value. Increasing doses of secretin induced a dose related increase in calcium output. There was a close parallel between calcium and protein outputs, suggesting that the increase in calcium output reflected primarily an increase in the enzyme-associated fraction of pancreatic juice calcium. It is concluded that secretin stimulates pancreatic enzyme secretion in man probably by a direct action on the acinar cells.     

Effect of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide on pancreatic,hepatic and duodenal mucosal bicarbonate secretion in the pig

BACKGROUND AND METHOD: The potency of pituitary adenylate cyclase-activating polypeptide (PACAP) and the related vasoactive intestinal peptide (VIP) on pancreaticobiliary and duodenal mucosal bicarbonate secretion (DMBS) was studied in anaesthetized pigs. VIP, PACAP27 and PACAP38 were infused at doses of 250, 500, 1,000, 2,000 and 6,000 pmol/kg x h. RESULTS: Infusion of VIP in these concentrations increased the portal plasma concentrations of VIP from 9 to 102, 220, 600, 850 and 3,795 pM, respectively. At doses of 1,000 and 6,000 pmol/kg.h all three peptides significantly stimulated pancreatic bicarbonate secretion, VIP from 0.0 to 0.3 and 7.6 mmol/h, PACAP27 from 0.0 to 2.3 and 8.2 mmol/h, and PACAP38 from 0.0 to 0.2 and 7.4 mmol/h, respectively. Only during infusion of 6,000 pmol/kg.h did the three peptides elicit a significant increase in hepatic bicarbonate output. At this dose VIP increased hepatic bicarbonate output from 0.4 to 3.8 mmol/h, PACAP27 from 0.3 to 3.6 mmol/h, and PACAP38 from 0.1 to 1.4 mmol/h, respectively. Infusion of VIP (500, 1,000, 2,000 and 6,000 pmol/kg.h) dose-dependently and significantly enlarged DMBS from 0.09 to 0.19, 0.41, 0.54 and 0.53 mmol/h, respectively. A significant effect of PACAP27 and PACAP38 on DMBS was only obtained at a dose of 6,000 pmol/kg.h, and at this dose VIP-induced DMBS was 4- and 8-fold higher than that induced by PACAP27 and PACAP38, respectively. CONCLUSIONS: VIP, PACAP27 and PACAP38 all have a pharmacological effect on both DMBS and pancreaticobiliary bicarbonate secretion. When comparing these results with the distribution of VIP/PACAP neurons and relevant receptors, it seems likely that VIP and PACAP have a physiological importance as neurotransmitters in the pancreas and duodenum, but not in the liver. The differences in the effect of VIP and PACAP on DMBS observed in this study indicate that there are variations between pancreatic and duodenal PACAP/VIP receptor subtypes, or that the duodenal inactivation of the peptides is different from the inactivation in the pancreas.     

Effects of glucagon, secretin, and vasoactive intestinal polypeptide on gastric somatostatin and gastrin release from isolated perfused rat stomach

To investigate the role of gastric somatostatin on gastrin secretion, glucagon, secretin, and vasoactive intestinal polypeptide (VIP) were perfused in the isolated pancreas-spleen-duodenum deprived preparation of rat stomach. After a preperfusion with 4.6% dextran Krebs-Ringer bicarbonate buffer containing 5.5 mM glucose, glucagon, secretin, and VIP at the concentrations of 10(-8), 10(-7), and 10(-6) M were infused into the left gastric artery at a constant flow of 2 ml/min for 15 min. All glucagon, secretin, and VIP evoked dose-dependent increases of somatostatin secretion with a simultaneous dose-related decrease of gastrin release. Furthermore, a significant correlation was found between the increase of somatostatin release and the decrease of gastrin secretion induced by glucagon, secretin, and VIP. These results raise the possibility that the suppression of gastrin secretion induced by glucagon, secretin, and VIP may, at least in part, be mediated by local action of gastric somatostatin.     

Mechanisms of terbutaline-induced inhibition of exocrine pancreatic secretion in humans

Terbutaline, a selective beta 2-adrenoreceptor agonist, has recently been advocated as a potential agent for treating patients with pancreatic fistulae. In the present study, we attempted to quantify the presumed effects of terbutaline on exocrine pancreatic secretion in humans and to characterize possible mechanisms of action. In six healthy volunteers, the pancreas was stimulated by infusion of graded doses of secretin (15.5-250 ng/kg/h) or by infusion of secretin (15.5 ng/kg/h) plus graded doses of caerulein (3.3-30 ng/kg/h). The experiments were repeated in each subject without and with administration of terbutaline. Pancreatic secretion was assessed by a marker perfusion technique and plasma somatostatin and pancreatic polypeptide (PP) levels by radioimmunoassay. Terbutaline had no significant effect on secretin-stimulated pancreatic secretion, but significantly inhibited caerulein-stimulated pancreatic fluid secretion and trypsin output. Plasma somatostatin and PP levels were not affected by terbutaline. The inhibitory effect required the administration of pharmacologically large doses of terbutaline. We conclude that the weak inhibitory effect of terbutaline on exocrine pancreatic secretion is not mediated via somatostatin nor PP and that our data do not support a major role for beta-adrenergic mechanism as regulator of pancreatic secretion.     

Effect of regulatory peptides on the vagally stimulated lower esophageal sphincter pressure in pigs

The effect of vasoactive intestinal polypeptide (VIP), enkephalin, neuropeptide Y, gastrin, cholecystokinin, neurotensin, somatostatin, and thyrotropin-releasing hormone on the lower esophageal sphincter pressure (LESP) was studied in anesthetized pigs. The peptides were infused into the arterial supply of the lower esophageal sphincter in graded doses during electrical stimulation of the vagal nerve (9 V, 10 Hz, 3 msec). The vagally stimulated LESP was inhibited by VIP (0-40 pmol/kg/min) and enkephalin (0-200 pmol/kg/min) in a dose-dependent manner. The other peptides had no effect on the stimulated LESP regardless of the dose tested. The results suggest that VIP and enkephalin may influence the stimulated LESP under normal conditions and that the other peptides tested did not affect the physiological regulation of the LESP. Furthermore, the vagally stimulated LESP was inhibited by atropine (250 micrograms/kg intravenously) but not by guanethidine (1 mg/kg intravenously).     

Effect of fatty acid on secretin release and cholinergic dependence of pancreatic secretion in rats

We investigated the effects of oleic acid in the duodenum on pancreatic exocrine secretion and plasma secretin, and determined the role of cholinergic dependence on pancreatic secretion and secretin release in response to oleic acid in anesthetized rats. Oleic acid emulsion (pH 6.5) in three different doses of 0.06, 0.25, and 1 mmol/h was infused intraduodenally for 1 h with or without intravenous administration of atropine in a dose of 100 micrograms/kg/h. Intraduodenal administration of oleic acid resulted in significant increases in pancreatic juice volume and bicarbonate output, in a dose-related manner (p less than 0.001). Plasma secretin concentration caused dose-dependent elevation (p less than 0.001) by oleic acid, which correlated very well with bicarbonate output in response to oleic acid (p less than 0.001). Atropine inhibited pancreatic secretion including juice volume and bicarbonate output stimulated by oleic acid in each dose, statistically significantly (p less than 0.05-0.01), but did not affect plasma secretin concentration. Thus, we conclude that oleic acid in the duodenum stimulates pancreatic secretion and endogenous secretin release in rats, and that secretin release is not influenced by the cholinergic tone, although pancreatic secretory response is inhibited significantly.     

Effect of somatostatin 14 on pure human pancreatic secretion

While it is well known that large doses of somatostatin inhibit human pancreatic enzyme secretion, it is still unknown whether low doses are also effective and whether the peptide is able to inhibit bicarbonate production. Eight subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery were studied. Somatostatin was infused at progressively increasing rates of 0.05, 0.15, 0.45, and 1.35 g/kg/hr, for 30 min/dose, during pancreatic stimulation with secretin, 25 ng/kg/hr, and cerulein, 10 ng/kg/hr. Somatostatin, at the dose of 0.05 g/kg/hr (shown to produce blood levels similar to those measured after a meal) did not affect pancreatic secretion in any of the subjects. The successive three higher doses caused a significant and dose-dependent inhibition of protein concentration and output and of bicarbonate output. Bicarbonate concentration was slightly but significantly reduced only by the two highest doses of somatostatin. At each dose level, the inhibition of protein output was much more marked than the inhibition of bicarbonate output. The maximal inhibition of protein output (at 1.35 g/kg/hr somatostatin) was 73.9±5.4%, and that of bicarbonate output was 55.9±6.4%. The results demonstrate that: (1) the administration of somatostatin at a low dose level does not affect human exocrine pancreatic secretion, at least under the experimental conditions of this study; and (2) the administration of larger doses of somatostatin inhibits pancreatic secretion of both protein and bicarbonate dose-dependently. The inhibitory effect on protein output is significantly greater than that on water and bicarbonate production.     

Post-somatostatin rebound secretion of growth hormone is dependent on growth hormone-releasing factor in unrestrained female rats

To examine the characteristics of GH secretion following the termination of the infusion of somatostatin, unrestrained adult female Wistar rats were subjected to repeated infusions of somatostatin separated by 30-min control periods. When somatostatin was infused for 150 min at a dose of 3, 30 or 300 micrograms/kg body wt per h, the magnitude of the rebound GH secretion increased in a dose-dependent manner. The infusion of somatostatin at a dose of 300 micrograms/kg body wt per h for 60, 150 or 240 min progressively augmented the size of the rebound GH secretion. When an antiserum to rat GH-releasing factor (GRF) was injected i.v. 10 min before the end of the infusion, the peak amplitude of the rebound GH secretion (300 micrograms/kg body wt, 150 min) was reduced to less than 20% of that of control rats. The rebound GH secretion (300 micrograms/kg body wt per h, 150 min) was augmented by a bolus injection of human GRF (1 microgram/kg body wt). The combined effect of the end of infusion of somatostatin and a bolus injection of GRF on the amount of GH secreted was additive. The plasma GH response to GRF was completely inhibited when human GRF (3 micrograms/kg body wt per h) and somatostatin (300 micrograms/kg body wt per h) were infused simultaneously for 150 min. The magnitude of the rebound GH secretion following the termination of the co-administration was larger than that following the somatostatin infusion alone, but this rebound was not enhanced by a bolus injection of human GRF.(ABSTRACT TRUNCATED AT 250 WORDS)