Platelet-activating factor, 5-hydroxytryptamine, thromboxane A2, adenosine diphosphate and thrombin are known to activate platelets by stimulating calcium entry, but the nature of the entry pathways is unknown. We present the identification of single divalent cation channels from thrombin-activated human platelets. Membrane vesicles from unstimulated and thrombin-stimulated human platelets were incorporated in planar bilayers and unitary currents through single channels were measured. Divalent cation selective channels could only be demonstrated in thrombin-stimulated preparations. These channels share a number of properties in common with voltage-dependent calcium channels--a high degree of selectivity for divalent cations, a single channel conductance of about 10 pS (in 150 mM Ba2+) and sensitivity to blockade by inorganic calcium channel blockers such as Ni2+. In other respects, these channels are different as they are not voltage-dependent and are not blocked by 1,4-dihydropyridine calcium channel antagonists.

The contractile effect of norepinephrine (NE) on isolated rabbit bronchial artery rings (150-300 microns in diameter) and the role of alpha 1- and alpha 2-adrenoceptors (AR) on smooth muscle and endothelium were studied. In intact arteries, NE increased tension in a dose-dependent manner, and the sensitivity for NE was further increased in the absence of endothelium. In intact but not in endothelium-denuded arteries, the response to NE was increased in the presence of both indomethacin (Indo; cyclooxygenase inhibitor) and NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthase inhibitor], indicating that two endothelium-derived factors, NO and a prostanoid, modulate the NE-induced contraction. The alpha 1-AR antagonist prazosin shifted the NE dose-response curve to the right, and phenylephrine (alpha 1-AR agonist) induced a dose-dependent contraction that was potentiated by L-NAME or removal of the endothelium. The sensitivity to NE was increased slightly by the alpha 2-AR antagonists yohimbine and idazoxan, and this effect was abolished by Indo or removal of the endothelium. Similarly, contractions induced by UK-14304 (alpha 2-AR agonist) were potentiated by Indo or removal of the endothelium. These results suggest that NE-induced contraction is mediated through activation of alpha 1- and alpha 2-ARs on both smooth muscle and endothelium. Activation of the alpha 1- and alpha 2-ARs on the smooth muscle causes contraction, whereas activation of the endothelial alpha 1- and alpha 2-ARs induces relaxation through release of NO (alpha 1-ARs) and a prostanoid (alpha 2-ARs).

Testicular side effects of procarbazine (Proc: 50 or 200 mg/kg i. p.), vincristine (Vin: 0.15 or 0.6 mg/kg i.p.) or busulfan (Bu: 10 mg/kg p.o.) were examined by morphological methods 3 days, 1 week and weekly thereafter until week 10 after a single exposure. With Proc a degeneration of the germ cells, particularly of mid primary spermatocytes, was seen first. Morphogenesis of early spermatids was disturbed, especially of those subcellular elements depending on an intact RNA metabolism. Later, giant cells were frequent. Yin led first to a malformation of late spermatids and arrest of cell division of spermatocytes and especially of spermatogonia, indicating microtubule dysfunction. After 2 and 4 weeks Bu showed a disappearance of spermatogonia and early spermatocytes leading to a depletion of the germinal epithelium by maturation. Late effects were rather similar in all the groups.

The electromechanical effects of calcitonin gene-related peptide (CGRP) on intact and endothelium-denuded rabbit ophthalmic arteries were studied. CGRP inhibited norepinephrine (NE)-induced contractions. In intact arteries after washout of CGRP the contractile sensitivity to NE was increased. Conversely, in endothelium-denuded arteries, the relaxation induced by CGRP was prolonged, and after washout of CGRP the contractile sensitivity to NE was diminished. In intact arteries NE contractions were enhanced by NG-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelium-derived relaxing factor (EDRF) synthesis, and in the presence of L-NMMA, CGRP-induced relaxations resembled those seen in endothelium-denuded arteries. This result suggests that there is an increased EDRF synthesis in intact arteries during NE stimulation and that CGRP may inhibit either the synthesis or the activity of EDRF. High concentrations of CGRP hyperpolarized the smooth muscle membrane both in intact and endothelium-denuded arteries. Hyperpolarizations were blocked by glibenclamide, indicating that they are mediated by activation of ATP-sensitive K+ channels. However, glibenclamide had little effect on the CGRP-induced relaxation. These results suggest that in normal physiological conditions CGRP-induced relaxation of the rabbit ophthalmic artery is mediated mainly by mechanisms other than hyperpolarization.