Comparison of intravenous and intramuscular sincalide (C-terminal octapeptide of cholecystokinin) on gallbladder contraction in man

Isometric contractions of coho salmon (Oncorhynchus kisutch) gallbladder longitudinal muscle strips were recorded in response to porcine cholecystokinin (CCK), octapeptide of CCK (OP-CCK), desulfated octapeptide of CCK (ds-OP-CCK), porcine heptadecapeptide gastrins I and II, and pentagastrin. Peak tonic contraction amplitude and peak rhythmic contraction frequency were used to construct concentration-response curves for each peptide. Observed maximal responses to each peptide were not significantly different; therefore, all peptides tested were equal in efficacy. CCK, OP-CCK, and gastrin II were equipotent, and ds-OP-CCK and gastrin I were equipotent. Conclusions: 1) porcine CCK can stimulate contraction of the coho salmon gallbladder; 2) tonic and rhythmic contractile responses are elicited in coho salmon gallbladder by agonists; 3) coho salmon gallbladder muscle cannot distinguish between agonists that differ in the location of a sulfated tyrosyl residue at position 6 versus position 7 from the C-terminus; and 4) the results of this study are consistent with the hypothesis that coho salmon gallbladder muscle contains a relatively primitive CCK receptor.

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Bioactivity of cholecystokinin analogues: CCK-8 is not more potent than CCK-33

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.247.1.g105 ◽

1984 ◽

Vol 247 (1) ◽

pp. G105-G111 ◽

Cited By ~ 2

Author(s):

T. E. Solomon ◽

T. Yamada ◽

J. Elashoff ◽

J. Wood ◽

C. Beglinger

Keyword(s):

Guinea Pig ◽

Pancreatic Secretion ◽

Gallbladder Contraction ◽

Bathing Medium ◽

Structural Analogues ◽

Biological Actions

We determined the relative molar potencies of structural analogues of porcine cholecystokinin (CCK-39, CCK-33, CCK-8, and caerulein). Peptide concentrations delivered in infusates or present in bathing medium were measured by radioimmunoassay. The presence of albumin prevented loss of CCK-39 and CCK-33 from solution to a greater degree than loss of CCK-8 and caerulein from solution. As much as 10-fold differences in CCK-33 and CCK-39 concentrations were seen in albumin-containing versus nonalbumin-containing infusates. The potency estimates calculated from radioimmunoassay-corrected concentrations with CCK-8 as standard (potency 1.00) were canine pancreatic secretion in vivo: CCK-39 4.1, CCK-33 2.2, and caerulein 2.1; rat pancreatic secretion in vivo: CCK-39 2.1, CCK-33 5.4, and caerulein 5.4; rat pancreatic secretion in vitro: CCK-33 1.7, and caerulein 1.2; guinea pig gallbladder contraction in vivo: CCK-33 1.3, and caerulein 0.9; and guinea pig gallbladder contraction in vitro: CCK-33 1.8, and caerulein 5.8. Our data indicate that CCK-8 is not more potent than longer analogues and suggest that larger forms of CCK may be important mediators of the biological actions of CCK.

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Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit in humans

Regulatory Peptides ◽

10.1016/s0167-0115(00)80018-x ◽

2000 ◽

Vol 94 (1-3) ◽

pp. 9

Author(s):

Pius Hildebrand ◽

Lukas P. Degen ◽

Annette Collet ◽

Livio Rossi ◽

Fuping Peng ◽

...

Keyword(s):

Gastric Emptying ◽

Intestinal Transit ◽

Gallbladder Contraction ◽

Small Intestinal Transit ◽

Small Intestinal ◽

Grp Receptors

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Effects of cimetropium bromide on gallbladder contraction in response to oral and intraduodenal olive oil

European Journal of Clinical Pharmacology ◽

10.1007/bf00315412 ◽

1990 ◽

Vol 39 (4) ◽

pp. 369-372 ◽

Cited By ~ 3

Author(s):

L. Marzio ◽

F. Di Felice ◽

V. Celiberti ◽

O. Pieramico ◽

L. Grossi ◽

...

Keyword(s):

Olive Oil ◽

Gallbladder Contraction ◽

Cimetropium Bromide

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CCK-58 is the only detectable endocrine form of cholecystokinin in rat

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00523.2002 ◽

2003 ◽

Vol 285 (2) ◽

pp. G255-G265 ◽

Cited By ~ 56

Author(s):

Joseph R. Reeve ◽

Gary M. Green ◽

Peter Chew ◽

Viktor E. Eysselein ◽

David A. Keire

Keyword(s):

Trypsin Inhibitor ◽

Pancreatic Secretion ◽

Molecular Form ◽

New Method ◽

Molecular Forms ◽

Gallbladder Contraction ◽

Rat Blood ◽

Physiological Relevance ◽

Fasted Rats

CCK-58 differs from CCK-8 in patterns of expression of pancreatic secretion of fluid and amylase and gallbladder contraction. These differences have physiological relevance only if CCK-58 release is stimulated by nutrients entering the intestine and if CCK-58 circulates in sizeable amounts. In this study, we report that when radiolabeled CCK-58 is added to rat blood and plasma is formed, there is extensive loss and degradation of the radioactive peptide. Therefore, a new method was developed to minimize loss and degradation of this label. This method recovered >85% of the label with no detectable degradation. Furthermore, the optimized method recovered all unlabeled exogenous cholecystokinin molecular forms in >80% yields. Blood from fasted rats and rats in which cholecystokinin release was stimulated by the trypsin inhibitor camostat contained only CCK-58 (3.5 ± 0.5 and 17 ± 1.5 fmol/ml, respectively). Because CCK-58 predominates in the blood, this molecular form should be used in studies on the physiology and pathophysiology of cholecystokinin.

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Identification of key residues that cause differential gallbladder response to PACAP and VIP in the guinea pig

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00279.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. G76-G83 ◽

Cited By ~ 2

Author(s):

Muxin Wei ◽

Kotoyo Fujiki ◽

Eiji Ando ◽

Sumin Zhang ◽

Tsuyoshi Ozaki ◽

...

Keyword(s):

Guinea Pig ◽

Contractile Activity ◽

Pcr Analysis ◽

Rt Pcr ◽

Gallbladder Contraction ◽

Hybrid Peptides ◽

Vpac Receptors ◽

Pituitary Adenylate Cyclase ◽

Key Residues ◽

Receptor Mrnas

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) have opposite actions on the gallbladder; PACAP induces contraction, whereas VIP induces relaxation. Here, we have attempted to identify key residues responsible for their interactions with PACAP (PAC1) and VIP (VPAC) receptors in the guinea pig gallbladder. We synthesized PACAP-27/VIP hybrid peptides and compared their actions on isolated guinea pig gallbladder smooth muscle strips using isotonic transducers. [Ala4]- and [Val5]PACAP-27 were more potent than PACAP-27 in stimulating the gallbladder. In contrast, [Ala4, Val5]- and [Ala4, Val5, Asn9]PACAP-27 induced relaxation similarly to VIP. [Asn9]-, [Thr11]-, or [Leu13]PACAP-27 had 20–70% contractile activity of PACAP-27, whereas [Asn24,Ser25,Ile26]PACAP-27 showed no change in the activity. All VIP analogs, including [Gly4,Ile5,Ser9]VIP, induced relaxation. In the presence of a PAC1 receptor antagonist, PACAP(6–38), the contractile response to PACAP-27 was inhibited and relaxation became evident. RT-PCR analysis revealed abundant expressions of PAC1 receptor, “hop” splice variant, and VPAC1 and VPAC2 receptor mRNAs in the guinea pig gallbladder. In conclusion, PACAP-27 induces contraction of the gallbladder via PAC1/hop receptors. Gly4 and Ile5 are the key NH2-terminal residues of PACAP-27 that distinguish PAC1/hop receptors from VPAC1/VPAC2 receptors. However, both the NH2-terminal and α-helical regions of PACAP-27 are required for initiating gallbladder contraction.

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