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C B Chan

Publications and source records attributed to C B Chan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ultrastructural and secretory heterogeneity of fa/fa (Zucker) rat islets.

Many previous studies of obese rodents documented biochemical changes in pancreatic islets that contribute to hyperinsulinemia in vivo. Those studies used heterogeneous populations of islets, although the size of islets from obese rats ranges from < 100 to > 500 microm. Here, functional and morphological changes in size-sorted (< 125 and > 250 microm diameter) islets from obese Zucker (fa/fa) rats were correlated. Ultrastructural examination revealed that > 250 microm cultured islets had an increased number of immature secretory granules in the beta cells. The number of degranulated beta cells in > 250 and < 125 microm cultured islets from fa/fa rats was higher than in lean rat islets (33 vs 25%). The glucose EC50 values for cultured islets were 4.64 +/- 0.43, 7.9 +/- 0.70 and 7.29 +/- 1.64 mmol.l(-1) for > 250 microm, < 125 microm, and lean groups, respectively. Inhibition of insulin secretion by 10 mmol.l(-1) mannoheptulose was reduced by 50% in > 250 microm islets compared with small islets. Studies of individual beta cells by reverse hemolytic plaque assay revealed 3-fold more cells from > 250 microm islets were stimulated by 1.4 mmol.l(-1) glucose than cells from < 125 microm islets. We conclude that functional defects in mixed size populations of islets from fa/fa rats are mainly due to alterations in the large islets, whereas smaller islets have relatively normal function. Exposure to high glucose exacerbates morphological and functional differences of large islets, which could have important implications in the transition to noninsulin-dependent diabetes when beta cell insulin production is unable to compensate for hyperglycemia.

Animals↗
PubMed1997

Reduced sensitivity of fa/fa Zucker rats to adrenomedullin.

Rat adrenomedullin is a peptide vasodepressor that may be of importance in the pathogenesis of hypertensive disease. Because of the known link between obesity and hypertension, we hypothesized that decreased responsiveness to adrenomedullin might be seen in an obese rodent model. In this study, the in vivo vasodilator actions of exogenous adrenomedullin were compared in anesthetized lean (n = 7) and obese (fa/fa) Zucker rats (n = 8). Adrenomedullin dose dependently lowered mean arterial pressure in both phenotypes, but the half-maximal dose (ID50) was 2-fold higher in fa/fa rats (1.7 +/- 0.22 vs. 0.83 +/- 0.06 nmol/kg). Moreover, the duration of effect was markedly reduced in the fa/fa rats, to 1-2 min from about 5 min in the lean animals. There was no evidence for an increased rate of degradation of adrenomedullin in the fa/fa rats. Although the rats used in this study were not hypertensive, adrenomedullin had reduced sensitivity and duration of action. The evidence suggests possible defects at the target receptor or altered metabolism of adrenomedullin in obesity.

Adrenomedullin↗
PubMed1996

Effect of adrenalectomy on the development of a pancreatic islet lesion in fa/fa rats.

Adrenalectomy prevents development of obesity and hyperinsulinaemia in obese (fa/fa) Zucker rats, thereby implicating the hypothalamo- pituitary-adrenal axis in the pathogenesis of obesity. In this study glucose-induced insulin secretion and glucokinase activity were investigated in isolated islets from adrenalectomized and control obese and lean female rats. Islets from control fa/fa rats were more sensitive to glucose with a half-maximal effective concentration (EC50) of 6.1 +/- 2.0 mmol. 1(-1) compared with 10.6 +/- 2.7 mmol. 1(-1) for adrenalectomized fa/fa rat islets. Adrenalectomy did not alter the islet sensitivity to glucose in the lean rats (EC50 of 9.4 +/- 1.5 mmol.1(-1) and 9.3 +/- 2.0 mmol. 1(-1) for adrenalectomized and control lean rats respectively). Mannoheptulose did not inhibit insulin secretion from control obese rats; however at concentrations of 1.0 mmol. 1(-1) or more it significantly inhibited glucose-induced insulin secretion in adrenalectomized obese and lean, and control lean rat islets (P < 0.05). In adrenalectomized fa/fa islets the glucokinase Km was increased twofold compared with the control fa/fa rats (9.5 +/- 1.5 mmol. 1(-1) vs 5.0 +/- 1.5 mmol. 1(-1), respectively), but there was no significant change in glucokinase Km in the lean rat islets after adrenalectomy. Mannoheptulose (10 mmol.1(-1) caused a significant reduction in glucose phosphorylation in disrupted islets of adrenalectomized fa/fa and lean, and of control lean rats, but not of control fa/fa rats. These data demonstrate that development of abnormal regulation of glycolysis in pancreatic islet beta cells of fa/fa rats, as indicated by the insulin response to manno-heptulose and glucokinase activity, is dependent on an intact hypothalamo-pituitary-adrenal axis.

Adrenalectomy↗
PubMed1996

Use of genomic DNA probes for the diagnosis of acute sarcocystosis in experimentally infected cattle.

Two clones of 1.4 and 4.33 kilobase pairs (kbp) DNA inserts, were selected from a Sarcocystis cruzi sporozoite genomic library constructed in bacteriophage lambda gt10. These clones strongly hybridized with sporozoite and merozoite DNA and were evaluated as probes for detection of merozoite DNA in clinical samples. Of five calves in the experiment, four were each orally dosed with approximately 200,000 S. cruzi sporocysts; one calf served as non-infected control. Subsequently, blood was collected from the calves twice weekly for 3.5 months and fractionated into buffy coats, polymorphonuclear cells, and plasma. Total cellular DNA extracted from these fractions was dot blotted on nylon membranes and hybridized with the probes radiolabeled with [alpha-32P]dATP. The probes detected merozoites on Day 22 post infection in the buffy coats and intermittently from Day 25-39 in the granulocyte fraction. Parasitemia (i.e. merozoites in blood) was also detected by indirect fluorescent antibody technique (IFAT) and direct microscopy, Diagnosis of sarcocystosis in cattle using genomic DNA probes by dot blot hybridization provides an alternative method of detecting parasitemia that is more rigorous than the other two tests (IFAT, direct microscopy) which rely on morphology of the merozoite and visualization by the examiner. As probes detected merozoite DNA in the granulocyte fraction, polymorphonuclear cells may be involved in the pathogenesis of S.cruzi; however this hypothesis requires further study.

Animals↗
PubMed1996

KATP channel-dependent and -independent pathways of insulin secretion in isolated islets from fa/fa Zucker rats.

We hypothesized that altered insulin secretory patterns in obese (fa/fa) Zucker rats might be caused by changes in downstream stimulus-secretion coupling events, such as ATP-dependent potassium (KATP) channel activity. The functions of KATP-dependent and -independent pathways of insulin secretion were therefore compared in lean and fa/fa Zucker rat isolated islets. KATP channel function was normal in fa/fa rat islets, as assessed by responsiveness to direct channel inactivators glybenclamide and quinine and by the receptor-mediated response to epinephrine and somatostatin. Altered sensitivity to glucose and mannoheptulose were explained by upstream alterations in glucose metabolism documented earlier. Despite normal inactivation of KATP channels by ATP depletion of fa/fa rat islets, glucose-stimulated insulin secretion was not inhibited, leading to studies of a putative KATP-independent pathway. When islets were depolarized by incubating with 30 mM potassium and 0.25 mM diazoxide to bypass KATP channels, glucose elicited a concentration-dependent response in both phenotypes. This response required glucose metabolism and Ca2+, as proven by experiments with nonmetabolizable glucose analogs and calcium chelation, but was only partially inhibited by a glycolytic inhibitor. Intermediates or products of oxidative metabolism are likely involved because alpha-ketoisocaproate also elicited a KATP-independent insulin response. The pattern of responses was similar in lean and fa/fa rat islets, indicating that neither of these pathways explains the insulin secretion by fa/fa rat islets depleted of ATP. In conclusion, phenotype-related differences in KATP channel function were consistent with upstream changes in glucose metabolism in fa/fa rat islets. Further studies are required to understand the basis of insulin secretion in ATP-depleted islets from fa/fa rats.

Adenosine Triphosphate↗
PubMed1996

Modulation by glucose of insulin secretion and glucose phosphorylating activity in cultured pancreatic islets from obese (fa/fa) Zucker rats.

OBJECTIVE: In normal B-cells, glucokinase activity is regulated by glucose. We hypothesized that chronic exposure to low or high glucose levels would regulate glucokinase function and insulin secretion differently in islets of fa/fa compared with lean rats. SUBJECTS, DESIGN, and MEASUREMENTS: Islets isolated from lean and fa/fa rats (8-12 wk old) were cultured for 1-7 days in low (3.3 mM), moderate (12.5 mM) or supraphysiological (25.0 mM) glucose-supplemented medium. Sensitivity to glucose of hexokinase, glucokinase (by enzyme assay and kinetic analysis), and the insulin response (by radioimmunoassay) were assessed in each group of islets. RESULTS: Islets of fa/fa rats cultured in 12.5 mM glucose for 1-7 days demonstrated a left-shift in both the EC50 of the insulin response and the Km of glucokinase to glucose. The glucokinase Vmax of fa/fa rat islets was lower under all conditions tested, thereby limiting the potential increase in insulin secretion. When cultured in 3.3 mM glucose for 1-7 days, fa/fa rat islets retained responsiveness to glucose longer and the estimated EC50 for glucose actually declined. However, the glucokinase Km for glucose increased three-fold in both phenotypes cultured in low glucose. Lean and fa/fa rat islets cultured in 25.0 mM glucose demonstrated a paradoxical hypersecretion of insulin to basal glucose concentrations and desensitization to stimulation by high concentrations of glucose. Islets from fa/fa rats were more easily desensitized, with significant effects in 25.0 mM glucose by 3 days compared with 7 days for the lean rat islets. Culture in high glucose erased the phenotype differences in glucokinase Km that were observed in 12.5 mM glucose cultured islets. CONCLUSIONS: Differences in fa/fa rat islet glucokinase were observed only at moderate, near physiological glucose conditions. Glucokinase activity was similarly affected by low or high glucose in the two phenotypes, although differences in insulin secretion pattern were still detected, leading to the conclusion that factors other than glucokinase contribute to altered insulin secretion in the fa/fa rat. Further study of the glucose desensitization phenomenon in fa/fa rat islets might help unravel the factors that increase susceptibility to development of diabetes mellitus in some phenotypes.

Animals↗
PubMed1995

Identification of biochemical defects in pancreatic islets of fa/fa rats: a developmental study.

Adult obese (fa/fa) Zucker rats hypersecrete insulin in response to glucose and other secretagogues. Functional changes in islet alpha 2-adrenoceptors (8) and glycolytic regulation (9) have been reported. In this study, the development of these biochemical lesions in islets isolated from suckling (3 week old) and weanling (5 week old) lean and fa/fa rats was investigated and compared to results in adult animals. Glucose (15 mM)-induced insulin secretion was inhibited by mannoheptulose (MH) in lean (n = 8) but not fa/fa (n = 10) adult rats, indicating loss of sensitivity of glucokinase to competitive inhibition. Sensitivity to MH was somewhat reduced in the islets of 3- and 5-week-old fa/fa (n = 7 and 12) compared to lean (n = 15 and 9) rats, requiring 30-100 fold higher concentrations to achieve significant inhibition. At 3 weeks of age fa/fa rats did not differ from lean controls in either islet insulin content or body weight, but both parameters were increased in fa/fa rats by 5 weeks. The presence of altered alpha 2-adrenoceptor function in fa/fa rats could not be confirmed in this study. Unlike the previous report, prazosin did not antagonize alpha 2-agonist mediated inhibition of insulin secretion. The presence of defective regulation of the glycolytic pathway by mannoheptulose in suckling and weanling rats may contribute to development of hyperinsulinemia in fa/fa rats.

Aging↗
PubMed1995

Increased glucose phosphorylating activity correlates with insulin secretory capacity of male JCR:LA-corpulent rat islets.

In this study the glucose responsiveness of isolated, overnight-cultured islets of obese LA/N-corpulent (cp/cp) rats was compared with glucose phosphorylating activity to determine whether changes in the function of glucokinase could be identified. Islets from both male and female cp/cp rats showed a left-shifted concentration response to glucose, with EC50 values of 1.5 and 4.6 mM, respectively, compared with 9.2 mM for lean control islets. Islets from cp/cp rats were partially resistant to inhibition by mannoheptulose, a glucokinase inhibitor. Minimum inhibitory concentrations were 10 mM in cp/cp vs. 3 mM in lean rat islets. Glucose phosphorylating potential was markedly increased in islets of male cp/cp, but not female cp/cp, compared with lean rats. The maximal velocity (Vmax) of hexokinase was increased 5-fold, while the Km of glucokinase was significantly decreased, in male cp/cp compared with the lean control islets(3.6 vs. 35.2 mM). The Km for glucokinase was also decreased in female cp/cp rat islets (17.2 mM). The data from male cp/cp rat islets are consistent with the idea that increased glucose phosphorylation capacity can contribute to insulin hypersecretion and an extreme leftward shift in the concentration-response curve. However, other factors must also be considered because female cp/cp rats have moderately increased insulin secretory capacity without marked changes in total glucose phosphorylating capacity.

Animals↗
PubMed1995

beta-cell stimulus - secretion coupling defects in rodent models of obesity.

Hyperinsulinemia accompanies obesity in human patients and experimental rodent models and exacerbates insulin resistance, but the causes of increased insulin secretion remain obscure. This review examines progress in defining biochemical and molecular beta-cell defects that have elucidated in the past 5 years. Some defects, such as decreased glucose transport, decreased mitochondrial FAD-linked glycerophosphate dehydrogenase activity, and altered anomeric specificity for glucose, become evident only after onset of non-insulin-dependent diabetes mellitus. Thus, these defects are unlikely to play a role in the pathogenesis of hyperinsulinemia in obesity. Other biochemical changes, including increased glucokinase and (or) hexokinase function, increased glucose cycling, and altered regulation of intracellular Ca2+ are present in obese nondiabetic animals and may therefore contribute to development of hyperinsulinemia. Few developmental studies have been performed to correlate onset of defects with environmentally and genetically mediated control mechanisms of beta-cell function. However, the availability of new molecular biology techniques should facilitate identification of factors causing hyperinsulinemia in obesity.

Animals↗
PubMed1994

Effects of prostaglandins on gastrin release from canine antral mucosal cells in primary culture.

Evidence in vivo indicates that endogenous and exogenous prostaglandins can alter gastrin secretion. We have used primary cultures containing canine antral G-cells to study the cellular actions of prostaglandins on gastrin secretion, comparing the effects of prostaglandin E2 (PGE2) and its synthetic analogue enprostil. Enprostil (10(-10)-10(-6) M) inhibited gastrin secretion in response to bombesin, carbachol, and forskolin, the latter a receptor-independent activator of adenylate cyclase. This inhibition by enprostil was reversed by treatment with pertussis toxin (200 ng/ml, 8 h). However, enprostil did not inhibit the postreceptor stimuli 8-bromoadenosine 3',5'-cyclic monophosphate (10(-3) M), calcium ionophore A-23187 (10(-7) M), or 4 beta-phorbol 12-myristate 13-acetate (10(-8) M). In contrast, whereas PGE2 inhibited forskolin-stimulated gastrin release, PGE2 did not inhibit the response to carbachol or bombesin in control cultures. However, in pertussis toxin-treated cultures, PGE2 inhibition was reversed and, in contrast, the responses to bombesin, carbachol, and possibly forskolin were augmented. Indomethacin at a dose of 10(-5) M did not alter basal or bombesin-stimulated gastrin secretion. However, the somatostatin antibody CURE-S6 enhanced the response to forskolin and enhanced inhibition by PGE2, suggesting that endogenous somatostatin produced an inhibitory tone in these cultures and excluding the possibility that PGE2 acted via release of endogenous somatostatin. Our data suggest that in cultured antral cells gastrin release is regulated by inhibitory and stimulatory prostaglandin mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗
PubMed1993

Glucokinase activity in isolated islets from obese fa/fa Zucker rats.

Glucokinase (EC 2.7.1.2) activity of B-cells was measured in extracted pancreatic islets isolated from lean and obese fa/fa Zucker rats and maintained in primary culture overnight. Formation of [14C]glucose phosphoric esters from D-[U-14C]glucose was measured in the presence of unlabelled glucose from 0.05 to 0.50 mM for hexokinase (EC 2.7.1.1) activity, and 8.0-16.0 mM unlabelled glucose for glucokinase activity. Eadie-Hofstee analysis revealed that hexokinase kinetic parameters (Vmax and Km) for [14C]glucose phosphoric ester formation were similar in lean- and fa/fa-rat islets. For glucokinase, there was no difference in Vmax. between phenotypes. A non-significant tendency to increased sensitivity to glucose was noted in the fa/fa-rat islets (P = 0.13). In lean-rat islets, the glucokinase inhibitor mannoheptulose (3 mM) decreased Vmax. by 80% and increased the apparent Km from 3.3 +/- 0.7 mM to 12.2 +/- 2.0 mM (P < 0.05). There was no difference in Km or Vmax. in mannoheptulose-treated versus control islets from fa/fa rats. This lack of effect was consistent with reported effects of mannoheptulose on insulin secretion from fa/fa-rat islets [Chan, MacPhail and Mitton (1993) Can. J. Physiol. Pharmacol. 71, 34-39]. The data from glucose and mannoheptulose experiments support the hypothesis that glucokinase function is altered in fa/fa Zucker rats and may contribute to fasting hyperinsulinaemia in vivo in these animals.

Animals↗
PubMed1993

Ofloxacin susceptibilities of 5,667 Neisseria gonorrhoeae strains isolated in Hong Kong.

Of 5,667 strains of Neisseria gonorrhoeae isolated from the Government Social Hygiene (sexually transmitted disease) Clinics in Hong Kong from 1990 to 1992, there was a trend toward an increase in the percentage of strains resistant in vitro to 0.01 and 0.1 microgram of ofloxacin per ml, with 54.3 and 5.5% resistant strains, respectively, in January 1990, rising to 95.3 and 41.5%, respectively, in December 1992. The percentage of strains for which the MIC is > 1 microgram/ml remains stable, and no clinical failure has yet been seen. This trend of decreasing susceptibility warrants close monitoring when ofloxacin is used as first-line treatment for gonorrhea.

Gonorrhea↗
PubMed1993

Evidence for defective glucose sensing by islets of fa/fa obese Zucker rats.

The hypothesis that a defect in glucose sensing by islets of fa/fa Zucker rats contributes to hyperinsulinemia in these animals was tested. Islets from lean and fa/fa rats were isolated by collagenase digestion and step-density gradient purification and then cultured overnight in Dulbecco's modified Eagle's medium containing 12.5 mM glucose. Obese rat islets were more sensitive to hypoglycemic glucose levels with half-maximal effective concentration (EC50) of 5.6 mM compared with an EC50 of 8.2 mM for lean rat islets. In contrast, responsiveness of both phenotypes to alpha-ketoisocaproate and quinine was similar. Mannoheptulose did not inhibit insulin secretion from fa/fa islets, although inhibitors of later events in the stimulus-secretion coupling pathway were normally inhibited by iodoacetate and diazoxide. Finally, starvation in vivo and culture of islets in low glucose concentrations (5 mM) in vitro both decreased glucose-stimulated insulin secretion from lean but not fa/fa rat islets. We conclude that fa/fa rat islets have an exaggerated insulin response to hypoglycemic stimuli, possibly as a result of a defect in B-cell glucokinase function.

Adenosine Triphosphate↗
PubMed1992

Functional characterization of alpha-adrenoceptors on pancreatic islets of fa/fa Zucker rats.

Recently, a defect in pertussis toxin-independent actions of epinephrine on pancreatic B-cells of fa/fa Zucker rats was reported (Cawthorn and Chan (1991) Mol. Cell. Endocrinol. 75, 197-204). We now report studies of islet alpha 2-adrenoceptor function of fa/fa rats. Insulin and cAMP production by islets of obese rats were both inhibited by the alpha 2-adrenoceptor agonist clonidine. Calculated pD2 values for clonidine were 9.57 +/- 0.59 and 9.43 +/- 0.33 for lean and fa/fa rat islets, respectively. Yohimbine reversed clonidine effects equipotently in lean and obese rat islets (pA2 values of 7.48 +/- 0.57 vs 7.43 +/- 0.58). Unexpectedly, the alpha 1-antagonist prazosin stimulated insulin secretion from islets of obese but not lean rats. Functional characteristics of the alpha-adrenoceptors on fa/fa islets are thus similar to those recently designated alpha 2B. Altered expression of alpha-adrenoceptors on pancreatic islets of fa/fa rats may contribute to changes in the pertussis toxin-independent pathway of epinephrine action previously observed.

Animals↗
PubMed1991

Effect of pertussis toxin on islet insulin secretion in obese (fa/fa) Zucker rats.

We used isolated islets of lean and obese Zucker rats to determine whether inhibitory pathways mediated by pertussis toxin-sensitive guanyl nucleotide-binding (Gi) proteins contribute to hyperinsulinemia in obese rats. Epinephrine (10(-4) M) and somatostatin (10(-7) M) inhibited insulin secretion by +/- 75% in lean and fa/fa rats. Overnight culture of islets with pertussis toxin (300 ng/ml) enhanced insulin release more in lean (+/- 120%) than obese (+/- 60%) rats. In lean rats incubation of pertussis toxin-treated islets with epinephrine resulted in lower immunoreactive insulin release (p = 0.0005) than pertussis toxin-treated islets without epinephrine. However, in obese rats pertussis toxin treatment reversed this inhibition. Pertussis toxin completely reversed inhibition by somatostatin in both phenotypes. Galanin had no effect on insulin secretion. Cellular cAMP content was similar in lean and obese rats. Inhibitory hormones had no effect on cAMP production. We conclude that islets of obese rats respond normally to inhibitors of insulin release. Reversal of somatostatin-induced inhibition by pertussis toxin indicates normal function of Gi in obese rats. A subtle difference in sensitivity to pertussis toxin between lean and obese islets was noted.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Gastrin release in obese Zucker rats.

In this study, gastrin release in the obese Zucker rat was investigated by in vivo and in vitro experiments. Obese rats exhibited normal plasma gastrin levels at 3 weeks (preobese), were moderately hypergastrinemic at 3 months and severely hypergastrinemic at 5 months, compared to lean littermates. Following oral peptone, plasma gastrin levels doubled in both lean and obese rats. Basal and vagally stimulated gastrin release from perfused stomachs was greater in obese compared to lean rats and atropine had no effect on basal gastrin release in either group. Basal somatostatin release from the perfused stomach was found not to differ in both groups of animals. Morphological studies revealed an increase in the number of gastrin-containing G-cells in adult obese rats compared to lean littermates, but not in 3-week-old pups compared to lean littermates, indicating a strong correlation between cell number and plasma gastrin levels. These data indicate that the obese Zucker rat exhibits fasting hypergastrinemia in vivo, a condition which appears after weaning and increases in severity with age. Gastrin hypersecretion persists from the vascularly perfused stomach preparation. The basal hypergastrinemia of the obese Zucker rat is independent of a hyperactive postganglionic cholinergic drive but is associated with and probably causally related to an increase in antral G-cell numbers.

Animals↗
PubMed1988

Pertussis toxin-sensitive cholinergic inhibition of somatostatin release from canine D-cells.

Development of an enriched cultured cell system allowed us to investigate the mechanism of cholinergic inhibition of somatostatin release stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) and Ca2+-protein kinase C-dependent pathways of cell activation. After a 24-h culture on rat tail collagen, D-cells, quantified by immunohistochemistry, were 18-fold enriched compared with unelutriated dispersed cells. Somatostatin release from cultured cells was expressed as a percent of the somatostatin released by a specific stimulus in control cells. Under basal conditions release of somatostatin was 2.3 +/- 0.6% of the total cell content. Epinephrine (1 microM) and cholecystokinin octapeptide (10 nM) increased somatostatin release to 6.98 +/- 1.25 and 10.72 +/- 1.64%, respectively. Carbachol (1 microM) completely inhibited somatostatin release stimulated by epinephrine and reduced cholecystokinin octapeptide-stimulated release to 75% of control levels. Carbachol inhibition of the response to both epinephrine and cholecystokinin octapeptide was totally prevented by 5 h of treatment of the cells with pertussis toxin (300 ng/ml). Somatostatin release in response to the diterpene forskolin (10 microM), dibutyryl cAMP (300 microM), the phorbol ester beta-phorbol 12-myristate 13-acetate (0.1 microM), and the calcium ionophore A23187 (1 microM) was also inhibited by carbachol and prevented by pertussis toxin pretreatment. The ADP-ribosylase inhibitor isonicotinamide (1 mM) selectively blocked the effect of pertussis toxin without altering other stimulatory or inhibitory responses. These data are consistent with the view that carbachol inhibits somatostatin release at guanyl nucleotide-binding protein and/or another pertussis toxin-sensitive site.

Animals↗