I Guinea-pig ileum suspended in Krebs solution showed a continuous increase of tone which was lost by changing the bath fluid. Prostaglandin E2 was released from the ileum during incubation, and its concentration in the bath fluid appeared to correlate with the increase in tone.2 Supramaximal field stimulation (10 Hz) resulted in increased release of prostaglandin E2 from the ileum. At lower rates of stimulation, the increase in the release of E2 compared with the resting output was not significant. 3 Indomethacin (1 and 10 ,g/ml) produced a significant, dose-related reduction of the amount of prostaglandin E2 measured in the bath fluid at rest and with field stimulation. Indomethacin inhibited the contraction of the ileum during incubation in Krebs solution. 4 Indomethacin (10 and 20,ug/ml) had no significant effect on the release of acetylcholine during field stimulation, but reduced the resting output of acetylcholine-from guinea-pig ileum in some experiments. 5The results are discussed in the context of the role ascribed to prostaglandins as physiological modulators in transmitter release. No evidence for a prostaglandin-mediated negative feedback mechanism on acetylcholine release was obtained.

More than thirty years ago, i.e. in November 1961, I have become involved in the history of thalidomide, and up to the present day I have never lost contact with the problem. It is quite impossible to relate in one lecture (to present) the whole complicated story of the initial synthesis of the drug in 1954, of its marketing in 1957, its spread to many countries in Europe, Asia, Australia, America and Africa, and of the following epidemic of malformations of the limbs and of the ears, often accompanied by malformations of the internal organs. So I decided to restrict my account on the most essential aspects and to tell you more about my personal experience than about the extensive literature on the subject. Though the first child afflicted by thalidomide damage to the ears was born on December 25, 1956, it took about four and a half years before an Australian gynaecologist, Dr. McBride of Sydney, suspected that thalidomide was the cause of limb and bowel malformations in three children he had seen at Crown Street Women's Hospital. There are only conflicting reports unsubstantiated by documents on the reaction of his colleagues and the Australian representatives of Distillers Company, producers of the British product Distaval between June and December 16, 1961, when a short letter of McBride was published in the Lancet. Distillers Company in Liverpool had received the news from Australia on November 21, 1961, almost exactly at the same time as similar news from Germany.

Ligation of a coronary artery was performed in conscious rats whose sympathetic system activity had been altered by various treatments. β‐Adrenoceptor blockade with acute (0.2 mg kg−1 plus 0.1 μg kg−1 min−1) or chronic (50–60 mg kg−1 daily for 12 days) propranolol treatment had little effect on arrhythmias, or other responses to ligation. Abrupt withdrawal of chronic propranolol two days before ligation was also without effect. Reduction of sympathetic activity acutely with labetalol (5 mg kg−1), or chronically with adrenomedullectomy and 6‐hydroxydopamine treatment, accentuated the adverse effects of ligation. The results of this study suggest that, while activity of the sympathetic system is not detrimental during ligation in the conscious rat, it may be important for survival.

Isometric tension responses to neuropeptides were recorded from anococcygeus muscles isolated from male mice. This smooth muscle tissue is innervated by inhibitory nonadrenergic, noncholinergic nerves that resemble, ultrastructurally, the peptidergic neurons of the gastrointestinal tract; the physiological function of the anococcygeus is not known. Slow sustained contractions were produced by oxytocin (0.2-20 nM), , and [Arg]-vasotocin (0.4-100 nM); the mouse anococcygeus is, therefore, one of the few examples of nonvascular smooth muscle from male mammals to respond to low concentrations of oxytocin and related peptides. Substance P (0.5-8 ,AM) caused distinctive, biphasic increases in muscle tone of some, but not all, preparations. Other neuropeptides producing contractions were neurotensin (2-100 ,uM) and thyrotropin-releasing hormone (2-100 ,AM); the responses were of similar time course and displayed selective cross-desensitization, suggesting that these two peptides act through a common distinct mechanism. Tetradecapeptide somatostatin (10-80 pM) and its analog urotensin 11 (0.1-5 ,uM), a dodecapeptide from the urophysis of the teleost fish Gilichthys mirabilis, produced similar slowly developing relaxations of carbachol-induced tone. Piscine urotensin II, of which there are no reported effects on nonvascular mammalian systems, was 20-50 times more potent than somatostatin, a well-established mammalian hormone. Of the peptides studied, only vasoactive intestinal polypeptide (0.05-1 ,uM) caused rapid powerful relaxations in low concentrations; this is consistent with its proposed involvement in nonadrenergic, noncholinergic neurotransmission in the mouse anococcygeus.The anococcygeus muscles are two thin sheets of smooth muscle that arise, separately, from tendonous origins on the posterior sacral vertebrae and run caudad around both sides of the rectum to unite on its ventral aspect; a physiological function of the tissue has yet to be elucidated (1). The muscles of all species studied to date (rat, cat, rabbit, dog, mouse, and ox) are innervated by motor sympathetic fibers, of which the transmitter is norepinephrine, and by inhibitory nonadrenergic, noncholinergic (NANC) fibers, of which the transmitter is unidentified (1-6). Ultrastructurally, the NANC nerves of the anococcygeus resemble the p-type fibers of the gastrointestinal tract, suggesting that the transmitter may be a peptide (7). It has been proposed recently that vasoactive intestinal polypeptide (VIP) might be involved in NANC transmission in the mouse anococcygeus (8). However, NANC relaxations of the mouse anococcygeus in response to field stimulation are complex, and it is possible that there is more than one NANC transmitter in this tissue (9). Consequently, we have investigated the effects of a wide range of neuropeptides on tone of the mouse anococcygeus in vitro. The anococcygeus muscle is unusually sensitive to substances that act by releasing norepinephrine from sympathetic nerve endings (1). To prevent such effects, each pre...