Actions of galanin and some of its analogues on rat isolated gastric fundus *

Summary— The study was undertaken to characterize the effects of porcine galanin (pGal) and some of its analogues on rat gastric fundus muscle strips. pGal, galantide (M15) and pGal(1–14)‐[Abu8]SCY‐I evoked reproducible concentration‐dependent contractions in concentrations of 1–300, 3–1,000 and 100–3,000 nM, respectively, with EC50 values of 13, 70 and 187 nM. Hill's coefficient for pGal is 1.03, indicating an interaction of one pGal molecule with one receptor, fulfilling criteria of classical receptor theory. For M15 and pGal(1–14)‐[Abu8]SCY‐I, Hill's coefficients are significantly different from 1, namely 0.73 and 1.56, so that one drug molecule may not interact with one receptor. The stimulatory effects of pGal were not modified by dibenamine 10 μM or glybenclamide 1 or 10 μM. Diltiazem 0.1, 1 and 10 μM, papaverine 0.1, 10 μM or dibutyryl cAMP (dib cAMP) 100 and 300 μM, blocked the contraction to pGal in a concentration‐dependent manner, indicating an important role for the influx of extracellular calcium ions and regulation by cAMP the pGal‐evoked contraction. Diltiazem, dibutyryl cAMP and papaverine were not competitive antagonists of pGal in the stomach smooth muscle.

[1]  Andrew P. Somlyo,et al.  Signal transduction and regulation in smooth muscle , 1994, Nature.

[2]  R. Jensen,et al.  Chimeric galanin analogs that function as antagonists in the CNS are full agonists in gastrointestinal smooth muscle. , 1993, The Journal of pharmacology and experimental therapeutics.

[3]  G. Sanger,et al.  The Effects of Various Peptides on Human Isolated Gut Muscle , 1992, The Journal of pharmacy and pharmacology.

[4]  J. Stull,et al.  Regulation of the Ca2+ dependence of smooth muscle contraction. , 1992, The Journal of biological chemistry.

[5]  T. Bártfai,et al.  The novel high-affinity antagonist, galantide, blocks the galanin-mediated inhibition of glucose-induced insulin secretion. , 1992, European journal of pharmacology.

[6]  V. Pieribone,et al.  M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Weiss,et al.  Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle. , 1991, Circulation research.

[8]  W. Creutzfeldt,et al.  Effects of galanin, its analogues and fragments on rat isolated fundus strips , 1990, British journal of pharmacology.

[9]  D. Coy,et al.  Galanin binding sites in rat gastric and jejunal smooth muscle membrane preparations , 1990, Peptides.

[10]  S. Bloom,et al.  Inhibitory effect of galanin on postprandial gastrointestinal motility and gut hormone release in humans. , 1989, Gastroenterology.

[11]  P. Lebrun,et al.  Galanin: Ca2+-dependent contractile effects on the isolated mouse distal colon. , 1989, European journal of pharmacology.

[12]  O. Petersen,et al.  Galanin activates nucleotide‐dependent K+ channels in insulin‐secreting cells via a pertussis toxin‐sensitive G‐protein. , 1989, The EMBO journal.

[13]  M. Laburthe,et al.  Mechanism of galanin-inhibited insulin release. Occurrence of a pertussis-toxin-sensitive inhibition of adenylate cyclase. , 1988, European journal of biochemistry.

[14]  M. Laburthe,et al.  Mechanism of galanin-inhibited insulin release , 1988 .

[15]  G. Mengozzi,et al.  An analysis of the effects of galanin on gastric acid secretion and plasma levels of gastrin in the dog. , 1988, European journal of pharmacology.

[16]  V. Chan‐Palay.  Galanin hyperinnervates surviving neurons of the human basal nucleus of meynert in dementias of alzheimer's and parkinson's disease: A hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia , 1988, The Journal of comparative neurology.

[17]  M. Lazdunski,et al.  ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by galanin, a hyperglycemia-inducing hormone. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  H. Imura,et al.  Central galanin stimulates pituitary prolactin secretion in rats: Possible involvement of hypothalamic vasoactive intestinal polypeptide , 1987, Neuroscience Letters.

[19]  L. Thim,et al.  Scyliorhinin I and II: two novel tachykinins from dogfish gut , 1986, FEBS letters.

[20]  W. Samson,et al.  Galanin: Evidence for a hypothalamic site of action to release growth hormone , 1986, Peptides.

[21]  G. Greenberg,et al.  Galanin Inhibits Insulin Secretion and Induces Hyperglycemia in Dogs , 1985, Diabetes.

[22]  H. Karaki,et al.  Comparative effects of verapamil and sodium nitroprusside on contraction and 45Ca uptake in the smooth muscle of rabbit aorta, rat aorta and guinea‐pig taenia coli , 1984, British journal of pharmacology.

[23]  Hans Jörnvall,et al.  Galanin — a novel biologically active peptide from porcine intestine , 1983, FEBS letters.

[24]  H. Ozaki,et al.  EFFECTS OF CALMODULIN ANTAGONISTS ON TENSION AND CELLULAR CALCIUM CONTENT IN DEPOLARIZED VASCULAR AND INTESTINAL SMOOTH MUSCLES , 1982, British journal of pharmacology.

[25]  W D PATON,et al.  The principles of drug action. , 1960, Proceedings of the Royal Society of Medicine.

[26]  P. Rekowski,et al.  Galantide contracts rat isolated fundus strips , 1995 .

[27]  G. Kupryszewski,et al.  GALANIN AND ITS ANALOGUES : SYNTHESIS AND STUDIES OF THEIR AGONIST ACTIVITY ON SMOOTH MUSCLES , 1993 .

[28]  Z. Herman,et al.  Synthesis and biological activity in GPI test of scyliorhinin I and its analogues modified in position 8 by Leu, Sar and Pro residues , 1991 .

[29]  R. Tallarida,et al.  Manual of Pharmacologic Calculations , 1981 .