Different roles of histamine receptor subtypes in ampullar & isthmic segments of human fallopian tube.

We have studied the influence of both menstrual cycle phase and subtype-selective histamine antagonists on the contractions produced by histamine isolated in human fallopian tubes. Histamine produced tonic contractions of the isolated preparations of both the ampullar and isthmic segments of the human fallopian tube were analyzed. The effects of both histamine and its antagonists were not dependent on the phase of the menstrual cycle. The isolated preparations of the ampullar segment from post menopausal patients were not responsive on histamine. When responding, the ampullar segments were slightly more sensitive to histamine than the isthmic segments. All three subtype selective histamine antagonists (pyrilamine, cimetidine and thioperamide) produced strong inhibition of histamine evoked contractions of the ampullar segment. On the other hand, only pyrilamine strongly inhibited histamine evoked contractions of the isthmic segment. The results of our study suggest that only H1 receptors were responsible for the histamine contractile effect on the isthmic segment and that all three subtypes of histamine receptors were involved in the effect of histamine on the ampullar segment of human fallopian tube.

Pharmacologic characterization of muscarine receptor subtypes in rat gastric fundus mediating contractile responses.

The role of four muscarinic receptor subtypes M1, M2, M3 and M4 which have been characterized pharmacologically was examined in motility control of isolated rat gastric fundus. Acetylcholine produced concentration-dependent tonic contraction of isolated rat fundus (EC50 = 9.64 +/- 0.14 x 10(-8)M). These contractions were concentration-dependently antagonized by atropine (KB = 2.45 x 10(-11)M), M1 selective blockers telenzepine (KB = 6.64 x 10(-11)M) and pirenzepine (KB = 2.3 x 10(-8)M), and hexocyclium (KB = 2.82 x 10(-10)M). M3-selective blocker p-fluoro-hexahydro-sila-difenidol (pFHHSiD) was a less potent antagonist (KB = 2.3 x 10(-8)M), while M2 and M4-selective methoctramine produced only weak blockade of tonic contractions caused by acetylcholine (KB = 4.68 x 10(-6)M). These results suggest that only M1 and M3 muscarinic receptors have functional roles in motility control of rat gastric fundus, M1 receptors being more important.

Spasmogenic action of beta-lactam antibiotics on the gastrointestinal tract of experimental animals.

We have investigated the effects of beta-lactam antibiotics on isolated preparations of rat fundus, ileum, and the body of feline stomach. Isotonic changes of isolated preparations were recorded. Benzylpenicillin (EC50 = 1.31 +/- 0.13 x 10(-5) M), ampicillin (EC50 = 2.16 +/- 0.15 x 10(-5) M), cefotaxime (EC50 = 1.33 +/- 0.15 x 10(-5) M), ceftriaxone (EC50 = 4.39 +/- 0.13 x 10(-5) M) and ceftazidime (EC50 = 1.42 +/- 0.01 x 10(-3) M) produced concentration-dependent tonic contractions of rat fundus. Rat ileum and feline stomach did not respond on these substances. Lidocaine (2.3 x 10(-5) M) and physostigmine (1.0 x 10(-8) M) significantly potentiated contractions produced by benzylpenicillin. On the other hand, methysergide (1.4 x 10(-7) M) and atropine (9.6 x 10(-9) M) significantly blocked tonic contractions produced by benzylpenicillin. Effects of beta-lactam antibiotics on smooth muscle isolated preparations were tissue and species dependent, indicating selectivity of their action.