This study was designed to characterize the calcitonin gene-related peptide (CGRP) receptors mediating vasodilation in the rat isolated perfused kidney and to address the question as to whether amylin, a 37 amino acid peptide having about 50% overall sequence homology with CGRP, interacts with common CGRP receptors or acts via distinct amylin receptors. Human alpha-CGRP (h alpha CGRP) and human beta-CGRP, rat alpha-CGRP and rat amylin amide produced dose-related vasodilation of the perfused renal vascular bed with pD2 estimates of rat alpha-CGRP (10.8 +/- 0.2), h alpha CGRP (10.5 +/- 0.2), human beta-CGRP (10.5 +/- 0.2) and rat amylin amide (9.4 +/- 0.3). In contrast, the CGRP2 receptor-selective agonist [acetamidomethyl-cysteine2.7]h alpha CGRP (0.1 mumol) was inactive. The CGRP1-receptor antagonist, h alpha CGRP8-37 reversibly antagonized the vasodilator response induced by h alpha CGRP with an apparent pK1 of 8.03 +/- 0.21. The analog h alpha CGRP8-37 (1 microM) also reversibly inhibited submaximal responses to rat amylin amide. In contrast, rat amylin8-37 (1 microM) had no significant inhibitory effect either on rat amylin amide- or on h alpha CGRP-induced vasodilation (P > .05), showing that rat amylin8-37 does not have affinity for the CGRP1 receptor in this preparation. These data suggest that the predominant CGRP receptors in the rat renal vascular bed are of the CGRP1 type, and that the vasodilation induced by rat amylin amide is due to CGRP1 receptor activation.
The results presented in this Report on the Organization of Pharmacology in the United Kingdom are based on replies to questionnaires sent out in 1983. In addition to academic and industrial research and development (R&D) departments we also surveyed industrial departments of toxicology, sales, clinical liaison and medical information, as well as specialized research units with no formal teaching function. The overall response rate was 87%. Since the last Report in 1971, the total number of pharmacologists has doubled to 2220, and they are now almost equally distributed between Universities and Industry. The most striking feature has been a major (3 fold) increase in the total number of industrial pharmacologists to 1014. In contrast, there was only a 1.3 fold increase in the number (99) of pharmacologists in established academic posts, over half of which are in the new departments of clinical pharmacology. Of the established pharmacologists in academic departments only 8% were less than 30 years of age and 22% over 50, whereas in industrial R&D departments the corresponding figures were 44% and 6% respectively. Since 1971 the proportion of pharmacy graduates in established academic or industrial R&D posts has fallen from 30% to 13% but the proportion with a medical qualification is almost unchanged. In academic departments, there was a net loss of established staff during 1982 and 1983 compared with a net gain of almost 100 appointments in industrial departments. The major single cause of academic pharmacologists leaving posts was early retirement, whilst in the industrial sector the major single destination was another industrial department. In 1983, 227 students graduated with a special B.Sc. degree in Pharmacology compared with 67 in 1971. The same period saw a decline in pharmacy students specializing in pharmacology (293 to 204) and the emergence of Joint Honours courses that include pharmacology. Pharmacology students who graduated in 1983 were also sent a questionnaire. From those responding (57%) over 90% were satisfied with their course and over 80% considered it adequate preparation for their future occupation. At the time of the survey in 1983, only 8% of students graduating in 1982 were unemployed, but all of the 1982 postgraduates were employed.
Abstract— Amino acids may be involved in primary afferent excitatory neurotransmission in the spinal cord. To test this possibility the effect of chronic dorsal root section on amino acid levels of the rabbit spinal cord has been investigated. Dorsal roots L6‐S2 were sectioned under anaesthesia. Control animals were subjected to similar surgical procedures but the dorsal roots were left intact. Electromyogram recordings taken 6 days after surgery confirmed the absence of sensory input to the lower lumbosacral cord of dorsal root sectioned animals although motor function was retained. In contrast to this control animals exhibited normal reflex activity. The spinal cord was removed from each animal and extracted in trichloracetic acid for subsequent analysts of amino acids on an autoanalyser. Sections of cord were retained for histological determination of neuronal degeneration. Comparison of amino acid levels in dorsal root sectioned and control animals revealed that the only excitatory amino acid to be significantly reduced by dorsal root section wasaspartic acid (–50 percent X although glutamic acid was also reduced (– 30 per cent). Two inhibitory amino acids, cystathionine and GABA, were also significantly depleted (– 50 and ‐ 35 per cent). The possible involvement of these amino acids in spinal cord neurotransmission is discussed.
The potencies of two tachykinin antagonists [D‐Pro 4 , D‐Trp 7,9,10 ]‐SP (4–11) and [D‐Arg 1 , D‐Pro 2 , D‐Trp 7,9 , Leu 11 ]‐SP (1–11) against four tachykinins were examined in a range of smooth muscle preparations, including guinea‐pig ileum and bladder and rat colon muscularis mucosae and duodenum. Parallel shifts in the log dose‐response curves of all the tachykinins tested were observed in all tissues, except in the case of the guinea‐pig bladder where [D‐Pro 4 , D‐Trp 7,9,10 ]‐SP (4–11) was without effect at concentrations up to 32 μM. The slopes of the Schild plots for the two antagonists did not differ significantly from unity, with the exception of [D‐Pro 4 , D‐Trp 7,9,10 ]‐SP (4–11) in the rat duodenum, which may indicate a heterogeneous receptor population in this tissue. The antagonists displayed agonist selectivity in the case of the guinea‐pig ileum where log dose‐response curves to substance P and physalaemin were shifted less than those to eledoisin and kassinin. Rank orders of potency for eledoisin, kassinin, physalaemin and substance P in the five preparations studied allowed classification of the tissues by the predominant receptor type according to the ‘SP‐P’ and ‘SP‐E’ scheme. It is concluded that [D‐Pro 4 , D‐Trp 7,9,10 ]‐SP (4–11) , in particular, displays tissue selectivity that may indicate different receptor populations, but classification of receptor and tissue types on this basis does not fully correspond with classifications based on agonist potencies. Such schemes should therefore be treated with caution at this stage.
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